Early manifestations of autism spectrum disorders. Experience of 393 cases in a child neurological centre

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Experience of 393 cases in a child neurological centre" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "414" "paginaFinal" => "420" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Bravo Oro, J. Vázquez Briseño, C.A. Cuello García, R.F. Calderón Sepúlveda, A.M. Hernández Villalobos, C. Esmer Sánchez" "autores" => array:6 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Bravo Oro" "email" => array:1 [ 0 => "antoniobravooro@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Vázquez Briseño" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "C.A." 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"apellidos" => "Esmer Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Departamento de Neuropediatría, Hospital Central Dr. Ignacio Morones Prieto, San Luís Potosí, S.L.P., Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Neuropediatría, Hospital Regional de Alta Especialidad del Bajío, León, Gto., Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Pediatría e Investigación Clínica, Escuela de Medicina, Instituto Tecnológico y de Estudios Superiores de Monterrey (ITESM), Monterrey, N.L., Mexico" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Neuropediatría y Neuropsicología, Centro Neurológico para Niños y Adolescentes (CENNA), Monterrey, N.L., Mexico" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Neuropsicología, Centro Neurológico para Niños y Adolescentes (CENNA), Monterrey, N.L., Mexico" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Departamento de Genética, Hospital Central Dr. Ignacio Morones Prieto, San Luís Potosí, S.L.P., Mexico" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Manifestaciones iniciales de los trastornos del espectro autista. Experiencia en 393 casos atendidos en un centro neurológico infantil" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1065 "Ancho" => 1477 "Tamanyo" => 58185 ] ] "descripcion" => array:1 [ "en" => "Number of new cases of autism spectrum disorders per year." ] ] ] "textoCompleto" => "IntroductionPervasive developmental disorders (PDDs) or autism spectrum disorders (ASD) are groups of disorders originating in the prenatal period and caused by abnormalities in the formation and functioning of neural circuits. These disorders are clinically and aetiologically heterogeneous.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Their main symptoms are deficiencies in the capacity for reciprocal social interaction, together with verbal and non-verbal communication deficiencies, abnormal interests, and repetitive and restrictive behavioural patterns.<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a>The Swiss psychiatrist Bleuler first used the term ‘autism’ in 1912 to refer to paediatric patients with schizophrenia.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> In 1943, Kanner and Asperger used the term independently to describe paediatric patients with communication problems.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a> When the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) was published in 1980, it included PDD and its diagnostic criteria, rather than the concept of ‘infantile psychosis’ which had been included in earlier versions.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>Recently, 5 forms of PDDs were added to the 10th edition of the International Classification of Diseases (ICD-10) and the latest edition of the DSM-IV-TR. The first form is autism, characterised by severe deficiencies in the areas of social interaction, language, communication, and play, in addition to stereotyped movements, repetitiveness, and little interest in ordinary activities. The second form is Asperger syndrome, in which mental abilities and language are intact in most cases, but socialisation is notably deficient and the patient has little interest in ordinary activities. A third category is Rett syndrome, which as an X-linked dominant disorder mainly affects girls. Patients with this disorder present acquired microcephaly, regression, loss of purposeful use of hands, stereotyped hand motions, severe developmental delays, and other neurological problems. The last 2 categories are PDD-NOS (not otherwise specified), in which children display autistic behaviours without meeting the criteria for placement in one or another of the disorders in the spectrum, and childhood disintegrative disorder, in which psychomotor development is normal but regression with a loss of cognitive ability occurs between 2 and 10 years of age.<a class="elsevierStyleCrossRefs" href="#bib0040">8,9</a>Recent epidemiological studies point to a potential increase in cases of autism; for example, in 1985, studies estimated approximately 5 cases per 10 000 individuals, while new estimates report 1 case per 100 children and adolescents.<a class="elsevierStyleCrossRefs" href="#bib0050">10–14</a>Early diagnosis in a patient with PDD is particularly difficult. However, when a complete neurological screening is performed in the first year of life, doctors can identify 40% of all children with a PDD.<a class="elsevierStyleCrossRefs" href="#bib0075">15–17</a>In this study, we describe the main neurological manifestations and age of diagnosis in 393 patients with different types of PDDs. We also analysed the yearly number of new cases at a centre specialising in care for children with neurological problems.Patients and methodsSubjectsWe reviewed all consecutive files pertaining to patients diagnosed with a PDD and examined in CENNA, the neurological centre for children and adolescents in Monterrey (Nuevo León) Mexico, between 1968 and 2009. We included all cases with at least 1 consultation with a specialist in paediatric neurology and a neuropsychological assessment confirming the diagnosis of PDD.For cases recorded between 1980 and 1987, we applied DSM-III diagnostic criteria; for cases from 1987 to 1994, DSM-III-R; for cases from 1994 to 2000, DSM-IV criteria; and after 2000, DSM-IV-TR criteria.AssessmentsWe began by listing the reasons why cases had been referred to our centre and recorded patients’ medical histories, age, sex, and the results of different neurological assessments. Reasons for referral were defined as follows.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">a.Speech impairments; language problems affecting either verbal communication (echolalia, prosodic abnormality, incomprehensible language, low vocabulary for the child's age, inability to begin or follow a conversation) or non-verbal communication (problems with body language, taking turns, and understanding sarcasm or jokes).</li><li class="elsevierStyleListItem" id="lsti0010">b.Language regression; progressive language loss.</li><li class="elsevierStyleListItem" id="lsti0015">c.Complete lack of language or speech, or use of incomprehensible sounds.</li><li class="elsevierStyleListItem" id="lsti0020">d.Socialisation problems, including cases of avoiding eye contact, problems developing interpersonal relationships, no desire to display or share interests, and poor expression of emotions.</li><li class="elsevierStyleListItem" id="lsti0025">e.Behaviour problems: harm to self or others, uneasiness, or lack of obedience.</li><li class="elsevierStyleListItem" id="lsti0030">f.Learning problems such as poor performance at school and difficulties with reading, writing, or mathematics.</li><li class="elsevierStyleListItem" id="lsti0035">g.Stereotyped behaviours, whether motor (flapping, swaying, or running in circles) or verbal (repeating words, phrases, or songs).</li><li class="elsevierStyleListItem" id="lsti0040">h.Psychomotor delay; delay in motor or psychosocial abilities identified with or without the use of standardised tests of any type.</li><li class="elsevierStyleListItem" id="lsti0045">i.Convulsions of any type.</li><li class="elsevierStyleListItem" id="lsti0050">j.Deafness.</li><li class="elsevierStyleListItem" id="lsti0055">k.Suspected PDD.</li></ul>The neuropsychological evaluation included an intelligence quotient (IQ) measurement using the Minnesota intelligence scale for children aged 18 months to 6 years; the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) for children aged 3 years and 10 months to 6 years and 7 months; and the Wechsler Intelligence Scale for Children, revised edition (WISC-R) for children aged 6 to 16 years.The diagnostic criteria for PDD were established based on the Childhood Autism Rating Scale (CARS, 1966), the Autism Spectrum Screening Questionnaire (ASSQ, 1981) by Lorna Wing, and the CENNA inventory of characteristics of autistic children (ICCAN-R, 1992).We used Schopler and Reichler's psychoeducational profile (PEP, 1972) to evaluate memory, language, visuospatial and visuoperceptual abilities, and fine and gross motor skills. Lastly, we used the Vineland Social Maturity Scale (1984) to measure children's level of social adaptation.We also analysed the age at which the child first came to the centre and the number of new cases per year. Statistical analysis was performed using the Excel® program by Microsoft® and predictive analytic software SPSS® version 18 (SPSS Inc., Chicago, IL). Data with a continuous distribution were expressed as means and standard deviations. Some categorical variables were contrasted using the chi-square test, or by using the t-test and analysis of variance (ANOVA) when examining more than 2 variables with a normal distribution. Binary logistic regression analysis was performed with presence or absence of each of the autism spectrum disorders as the dependent variable in order to detect any potentially significant associations with age at detection, sex, neuropsychological tests, or anomalies in the electroencephalogram (EEG).ResultsWe completed a retrospective and descriptive study of a series of 393 cases. In this study, we obtained data from the files of patients diagnosed with PDD according to the tools that were available at the time of diagnosis (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Classification of PDDThe most frequent category was autism, which accounted for 82.1% (n=323) of cases in the series, including 15 cases that were diagnosed before PDD was divided into categories. The next most common category (9.9%, n=39) was PDD-NOS; Asperger syndrome accounted for 4.8% (n=19), and Rett syndrome, 3% (n=12). There were no diagnoses of childhood disintegrative disorder.PDD was diagnosed in 6 patients using criteria predating DSM-III; in 9 patients using DSM-III criteria; in 62 patients using DSM-III-R criteria; in 160 using DSM-IV; and in 156 using DSM-IV-TR.Frequency of new cases per yearThe number of new cases per year is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. One of our goals was to determine whether or not age at the time of detection of PDD has decreased. However, the mean age at which autism spectrum disorders are identified did not vary with respect to the chronological year when we compared all of the mean ages at detection for each year using ANOVA (P=.13). The analysis was performed by dividing the sample into 10-year periods and 2 groups corresponding to before and after use of DSM-IV criteria; the mean and significance level remained the same.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Reasons for referralThe most common reasons for referral throughout the study population were language problems (absence, disorders, or regression of language), found in 58.7% of the cases, followed by behavioural problems in 16.2% of cases and socialisation problems in 7.6%. In 62.5% of the autism cases, the initial symptom was language disorder, whereas the initial symptom was behavioural and socialisation disorder in 68.4% of the cases of Asperger syndrome. Patients with Rett syndrome were most frequently referred due to psychomotor delays (41.7%) and language regression (25%); these 2 motives for concern accounted for 8 of the 12 patients. Reasons for referral are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> (neuropsychological evaluations).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Intelligence quotient was measured in 309 autistic patients; scores of 69 or less were found in 227, meaning that intellectual disability was present in 73.5% (95% confidence interval, 68.5%–78.4%) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). None of the patients with Asperger syndrome had intellectual disability and their mean IQ score was 103 (range, 77–118). All patients with Rett syndrome had moderate to severe intellectual disability. Intellectual disability was also present in 46.9% of the patients with PDD-NOS (95% confidence interval, 31.2–62.5).Distribution by sex and ageAges at which PDD was detected ranged from 4 months to 15 years, with a mean of 4.4 years. The mean age in the autistic patient group was 4.1 (±2.15) years. All patients with Asperger syndrome were male, and their mean age at diagnosis was 8 years (±3) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). As would be expected, all 12 patients with Rett syndrome were female. Age at detection and sex distribution were significantly different in this category (P=.01) compared to other categories in the autism spectrum.Other neurological findingsIn 4.5% of cases, patients were referred due to experiencing seizures and were later diagnosed with a PDD. EEG was performed on 78 of the 393 patients (19.8%); 37 EEGs (47.4%) revealed an anomaly. Other diseases in addition to the autism spectrum disorder were diagnosed in 3.8% of cases. These included 7 cases of idiopathic epilepsy, 3 cases of tuberous sclerosis, 2 cases of Lennox–Gastaut syndrome, 1 of hypomelanosis of Ito, and 1 of microcephaly.DiscussionOur study is one of the first to analyse the distribution of patients with autistic traits. It supports existing literature in that it finds classical forms of autism to be predominant, while other categories, such as Asperger or Rett syndrome, account for less than 10% of the total cases.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>In recent decades, there has been an increase in the number of children diagnosed with PDD. This increase appears to be linked to better knowledge of the symptoms of the disorder and the development of new diagnostic tools. The gold standard evaluations for diagnosing PDD are DSM-IV, the autism diagnostic observation schedule (ADOS), and the revised autism diagnostic interview (ADI-R).<a class="elsevierStyleCrossRef" href="#bib0070">14</a>The increase in PDD prevalence is a controversial topic worldwide. Various theories have been used to try to explain this phenomenon, including the shift toward the concept of the ‘autism spectrum’ rather than the concept of a single entity. This accounts for there being more patients with PDD.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Increased knowledge of autism among the general population may lead to parents, family members or health professionals suspecting such a disorder in young children.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> The current study was carried out in a paediatric neurology centre of reference in northern Mexico, and shows that a significant number of patients have been diagnosed with a PDD in recent decades. However, the prevalence of autism in Mexico is unknown. The strategy for measuring it could involve using a national system of records capable of demonstrating changes in the prevalence of this disorder in an epidemiologically valid way.Howlin et al. report that mean age of diagnosis in developed countries has dropped from 6.8 years to 2.7 years<a class="elsevierStyleCrossRef" href="#bib0100">20</a>; our study shows a mean age of 4 years at referral and diagnosis. Most of the patients suffer from lifelong disability which affects them directly and also has an impact on the dynamic of their families. Although evidence is limited in this area, the general consensus is that early intervention in PDD cases can improve multiple areas of the patient's quality of life.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>Casuistics are somewhat heterogeneous owing to the long time period spanned by the study. Conclusions regarding increases in the number of diagnoses were not easy to analyse due to diagnostic criteria having changed during the study period. This is also problematic when we make comparisons to determine whether disorders are being diagnosed earlier. Even when groups are divided up by decades, half-decades, or by diagnosis before or after publication of DSM-IV criteria, the mean age at diagnosis remains approximately 4 years.One relevant finding from our study is that language disorders were the initial symptoms of autism in 50%–60% of the cases. This figure is lower than the 80% reported by Tuchman et al. as the percentage of parents who observe language development problems in their autistic children.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> It is possible that language problems being detected later by both parents and primary care doctors would have contributed to the children in that series being diagnosed when they were older. We should also note that language disorders are not limited to patients with PDD. They may be associated with intellectual disability, or be classified as developmental or specific language disorders.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> Differential diagnosis is clinical, and it confirms the presence of abnormalities in other cognitive and behavioural areas that would be typical of PDD. Performing a neuropsychological evaluation is extremely important if there are any doubts about the diagnosis. It also provides information about the patient's cognitive abilities.Our study highlights the need for longitudinal studies that evaluate how diagnosing a patient before age 2 may affect the patient's quality of life. Checking developmental milestones was only added to Mexico's guidelines for childhood disease prevention and management<a class="elsevierStyleCrossRef" href="#bib0120">24</a> a decade ago. However, it is clear that we need to develop more suitable screening methods for autism spectrum disorders and include them in the guidelines. This will enable the paediatrician, family doctor, nursing staff, and any other professionals in charge of well-child care to recognise signs of PDD and diagnose them as early as possible so that the child can come under the care of a multidisciplinary group of experts. The primary care doctor must be able to recognise suspicious behaviour or signs in order to begin the process of diagnosing and then treating the condition. Recent studies suggest that clinical signs that may point to autism in children younger than 2 years include absence of response when called by name, lack of reciprocal play, lack of motor imitation (does not copy the motor movements of others), problems interacting with others (does not point fingers or try to attract another person's attention), and responding with gestures.<a class="elsevierStyleCrossRefs" href="#bib0115">23,25</a>Psychomotor development problems are common in patients with PDDs. Identifying such problems in patients will have important repercussions for making decisions regarding treatment. We found intellectual disability in 73.5% of the cases, a similar percentage to that reported by other authors.<a class="elsevierStyleCrossRefs" href="#bib0130">26,27</a> This demonstrates the need to rule out PDD in patients initially diagnosed with mental retardation.The prevalence of epilepsy in PDD patients ranges from 6% to 38% according to some authors.<a class="elsevierStyleCrossRefs" href="#bib0140">28–30</a> Certain forms of epilepsy such as Landau–Kleffner syndrome, West syndrome and continuous spikes and waves during slow sleep are associated with PDD. This is why EEGs should be performed, especially in patients displaying neurological regression. We must thoroughly evaluate any cases that might benefit from anticonvulsants, since the frequency of abnormal EEG readings in patients with PDD and no clinical signs of seizures is about 45.5%.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> In our series, 78 patients had an EEG and 47.4% of those cases had abnormal EEG readings. This was somewhat higher than the rate reported in the literature; also, 4.5% were epileptic. Recent evidence shows that all patients with autism are likely to present abnormal EEG findings when they are analysed under certain conditions. These include poorer integration of the anterior–posterior plane than would be expected at the child's age, and increased neural noise caused by hyperexcitability of the primary somatosensory cortex. The latter may be related to the severity of symptoms of the disorder.<a class="elsevierStyleCrossRef" href="#bib0160">32</a>Although this is a retrospective study based on data from medical records with a moderate selection bias due to the type of institution, we believe it provides important information about the distribution of the different autism spectrum disorders, the age at which the disorder begins to be noticed by parents as a medical problem, and the main symptoms which cause parents to seek care in specialised centres.In defining PDDs as developmental disorders of the brain that may arise during the prenatal stage due to neuronal network dysfunction, we are considering a number of different causes, such as alterations in the cellular architecture of the central nervous system and/or neurotransmitters.<a class="elsevierStyleCrossRefs" href="#bib0165">33,34</a> The most relevant task in current research on autism is searching for aetiological and/or risk factors which, in the near future, will enable us to opt for specific molecular treatments for a disease which is currently severe, disabling, and incurable.In the past decade, available studies have shown that a wide variety of genetic mechanisms are involved in the aetiology of PDDs. Examples include monogenic disorders such as Rett syndrome; microdeletion or microduplication syndromes; anomalous imprinting; variations in the number of copies; and polymorphisms susceptible to the disorder.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> The autistic behavioural phenotype has been found in more than 100 genetic syndromes, including fragile X syndrome and tuberous sclerosis. Based on these findings, it is now proposed that PDDs be categorised as syndromic or non-syndromic. Even in non-syndromic cases, scientists have identified changes in the sequence or function of various genes, including NLGN3, NLGN4, PTEN, SHANK, etc. (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRefs" href="#bib0175">35,36</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The syndromic component of autism may be found in up to 40% of cases when diagnostic methods such as microarray-based comparative genomic hybridisation are used to identify small losses or gains in genetic material.<a class="elsevierStyleCrossRef" href="#bib0185">37</a>The cases in our study include 5 patients with hereditary diseases, highlighting the importance of genetic evaluation in cases with PDD. Recent guidelines for studying the genetic causes of PDDs are available. The American College of Medical Genetics published its recommendations in 2008, and the American Academy of Pediatrics published its own statement in 2010. Since they are so recent, these recommendations were not completely integrated in our study cases. Despite the fact that genetic studies are being developed and made available in many areas of the world, many countries, including Mexico, face both technological and economic barriers that prevent their routine use. In fact, the capacity to study the genetic causes of autism is even limited in highly specialised neurology centres.<a class="elsevierStyleCrossRefs" href="#bib0190">38,39</a> Our group decided to evaluate each PDD case in order to determine what type of study to request, rather than subjecting patients to full diagnostic panels that most of those treated in our centre would be unable to afford.PDDs are frequently seen in neurology centres. The aetiological perception of these entities has changed, and so have our means of diagnosing and treating them. The solution to providing total care for children with PDDs is twofold. In addition to promoting training for health professionals so as to improve their diagnostic accuracy, we also need infrastructure and staff trained to provide specialised care using the best resources at their disposal.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres169981" "titulo" => array:5 [ 0 => "Abstract" 1 => "Introduction" 2 => "Patients and methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec158056" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres169982" "titulo" => array:5 [ 0 => "Resumen" 1 => "Introducción" 2 => "Pacientes y métodos" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec158055" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Assessments" ] ] ] 6 => array:3 [ "identificador" => "sec0025" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Classification of PDD" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Frequency of new cases per year" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Reasons for referral" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Distribution by sex and age" ] 4 => array:2 [ "identificador" => "sec0050" "titulo" => "Other neurological findings" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-06-14" "fechaAceptado" => "2011-09-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec158056" "palabras" => array:6 [ 0 => "Autism spectrum disorders" 1 => "Language disorders" 2 => "Autism" 3 => "Neurodevelopmental delay" 4 => "Early detection" 5 => "Epidemiological data" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec158055" "palabras" => array:6 [ 0 => "Trastornos del espectro autista" 1 => "Problemas de lenguaje" 2 => "Autismo" 3 => "Trastornos del neurodesarrollo" 4 => "Detección temprana" 5 => "Aspectos epidemiológicos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "IntroductionThe autism spectrum disorders are group of conditions characterised by qualitative impairments in social communication; in the interaction and imagination; with a restricted range of interests and stereotyped repetitive behaviours. Frequently, there is a delay in the age of detection, and therefore in starting multidisciplinary evaluations and interventions, which may result in a worst prognosis and an impaired quality of life for both children and parents. The aim of our study was to describe some clinical and epidemiological data including the age of detection and main initial complaints present in children with autism disorders from a paediatric neurology centre. Patients and methodsA total of 393 medical records of consecutive cases with a diagnosis of autism spectrum disorders were reviewed. ResultsAutism was diagnosed in 82.1% of the cases, unspecified pervasive disorder in 9.9%, and Asperger syndrome in 4.8%. Sixty percent of autistic children presented with a language disorder as their main complaint. The average age of detection was 4 years. ConclusionsCompared with other countries, age of detection is delayed. A Primary Care based screening and surveillance are required in order to improve prognosis and quality of life of children with an Autism Spectrum Disorder." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "IntroducciónLos trastornos del espectro autista son un grupo de desórdenes que se caracterizan por problemas en la socialización, en la comunicación verbal y no verbal; y por patrones de conducta repetitivos e intereses restringidos. La edad en la que se identifican varía según sea la intensidad e instalación de los síntomas iniciales del padecimiento. En las mejores condiciones de atención, las primeras manifestaciones se notan alrededor de los doce meses de edad y el diagnóstico se define entre los dos y tres años. Con frecuencia la búsqueda de atención médica y el inicio de las intervenciones se retrasan por la dificultad en la identificación de signos incipientes del trastorno. Los objetivos de nuestro estudio fueron describir las manifestaciones clínicas iniciales y aspectos epidemiológicos en pacientes con sospecha diagnóstica de espectro autista referidos a un centro neuropediátrico. Pacientes y métodosSe realizó análisis sistemático retrospectivo de 393 expedientes consecutivos con algún trastorno del espectro autista. ResultadosEntre los casos revisados 82,1% correspondieron al diagnóstico de autismo, 9,9% trastorno inespecífico, 4,8% Asperger y 3% con síndrome de Rett. El promedio de edad a su primera evaluación fue de 4,4 años. El 62,5% de los casos con autismo fueron detectados por problemas de lenguaje. ConclusionesLa edad de diagnóstico comparada con otros países sigue siendo tardía. Es necesario favorecer la detección temprana para mejorar el pronóstico y la calidad de vida de los niños con trastorno del espectro autista." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Bravo Oro A. et al. Manifestaciones iniciales de los trastornos del espectro autista. Experiencia en 393 casos atendidos en un centro neurológico infantil. Neurología. 2012;27:414–20." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1065 "Ancho" => 1477 "Tamanyo" => 58185 ] ] "descripcion" => array:1 [ "en" => "Number of new cases of autism spectrum disorders per year." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "N.A.: not available." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Autism (n=323) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Asperger syndrome (n=19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Rett syndrome (n=12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">PDD-NOS (n=39) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age in years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.1 (±2.15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (±3)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.6 (±3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.3 (±3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female patients (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (16.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (28) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intelligence quotient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 (±19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">103 (±13)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N.A. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 (±20) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intellectual disability (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">227 (73.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (46.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab264943.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Mean age and intellectual coefficient were significantly higher in cases with Asperger syndrome than in cases of other autism spectrum disorders." ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of pervasive developmental disorders." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Reasons for referral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Autism (n=323) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Asperger syndrome (n=19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Rett syndrome (n=12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">PDD-NOS (n=39) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lack of language (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 (25.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (15.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Language difficulties \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88 (27.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (21.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (30.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Language regression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (9.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Socialisation problems \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (6.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (36.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Behavioural disorder \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 (15.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (31.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (23.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Learning disorder \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stereotyped behaviours \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Psychomotor retardation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (41.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Seizures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (12.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hearing loss \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (0.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Referral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (2.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab264942.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Reasons for referral." ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gene (OMIM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Locus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Function \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Clinical phenotype \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NLGN3 (300336) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neuroligin-3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xq28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Synapse formation and function \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autism, Asperger, PDD-NOS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NLGN4 (300427) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neuroligin-4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xp22.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Synapse formation and function \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autism, Asperger, PDD-NOS, X-linked intellectual disability. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NRXN1 (600565) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neurexin-1α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2p16.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated with neuroligins \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autism with seizures and facial dysmorphism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SHANK3 (606230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SH3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22q13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Postsynaptic organisation and neuroligin binding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autism with severe language and socialisation deficiencies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HOXA1 (142955) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Homeobox Protein Hox A1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17p15.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Essential factor for head and neck growth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PDD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PTEN (601728) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phosphatidylinositol(3,4,5)-triphosphate 3-phosphatase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10q23.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absence causes increase in dendrites and axonal growth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PDD with macrocephaly \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mEcP2 (300005) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methyl-CpG binding domain protein 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xq28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Located in promoters and other proteins associated with chromatin repression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autism, Rett syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RELN (600514) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reelin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7q22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Marker of neuronal migration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autism and schizophrenia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UBE3A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ubiquitin-protein ligase E3A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15q11–q13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regulation of neuronal activation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PDD and Angelman syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab264941.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Genes involved in non-syndromic autism." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0005" 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Manifestaciones iniciales de los trastornos del espectro autista. Experiencia en 393 casos atendidos en un centro neurológico infantil

A. Bravo Oroa,

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antoniobravooro@hotmail.com

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, J. Vázquez Briseñob, C.A. Cuello Garcíac, R.F. Calderón Sepúlvedad, A.M. Hernández Villalobose, C. Esmer Sánchezf

a Departamento de Neuropediatría, Hospital Central Dr. Ignacio Morones Prieto, San Luís Potosí, S.L.P., Mexico

b Departamento de Neuropediatría, Hospital Regional de Alta Especialidad del Bajío, León, Gto., Mexico

c Departamento de Pediatría e Investigación Clínica, Escuela de Medicina, Instituto Tecnológico y de Estudios Superiores de Monterrey (ITESM), Monterrey, N.L., Mexico

d Departamento de Neuropediatría y Neuropsicología, Centro Neurológico para Niños y Adolescentes (CENNA), Monterrey, N.L., Mexico

e Departamento de Neuropsicología, Centro Neurológico para Niños y Adolescentes (CENNA), Monterrey, N.L., Mexico

f Departamento de Genética, Hospital Central Dr. Ignacio Morones Prieto, San Luís Potosí, S.L.P., Mexico

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Pervasive developmental disorders &#40;PDDs&#41; or autism spectrum disorders &#40;ASD&#41; are groups of disorders originating in the prenatal period and caused by abnormalities in the formation and functioning of neural circuits&#46; These disorders are clinically and aetiologically heterogeneous&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Their main symptoms are deficiencies in the capacity for reciprocal social interaction&#44; together with verbal and non-verbal communication deficiencies&#44; abnormal interests&#44; and repetitive and restrictive behavioural patterns&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The Swiss psychiatrist Bleuler first used the term &#8216;autism&#8217; in 1912 to refer to paediatric patients with schizophrenia&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In 1943&#44; Kanner and Asperger used the term independently to describe paediatric patients with communication problems&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> When the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders &#40;DSM-III&#41; was published in 1980&#44; it included PDD and its diagnostic criteria&#44; rather than the concept of &#8216;infantile psychosis&#8217; which had been included in earlier versions&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Recently&#44; 5 forms of PDDs were added to the 10th edition of the International Classification of Diseases &#40;ICD-10&#41; and the latest edition of the DSM-IV-TR&#46; The first form is autism&#44; characterised by severe deficiencies in the areas of social interaction&#44; language&#44; communication&#44; and play&#44; in addition to stereotyped movements&#44; repetitiveness&#44; and little interest in ordinary activities&#46; The second form is Asperger syndrome&#44; in which mental abilities and language are intact in most cases&#44; but socialisation is notably deficient and the patient has little interest in ordinary activities&#46; A third category is Rett syndrome&#44; which as an X-linked dominant disorder mainly affects girls&#46; Patients with this disorder present acquired microcephaly&#44; regression&#44; loss of purposeful use of hands&#44; stereotyped hand motions&#44; severe developmental delays&#44; and other neurological problems&#46; The last 2 categories are PDD-NOS &#40;not otherwise specified&#41;&#44; in which children display autistic behaviours without meeting the criteria for placement in one or another of the disorders in the spectrum&#44; and childhood disintegrative disorder&#44; in which psychomotor development is normal but regression with a loss of cognitive ability occurs between 2 and 10 years of age&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Recent epidemiological studies point to a potential increase in cases of autism&#59; for example&#44; in 1985&#44; studies estimated approximately 5 cases per 10 000 individuals&#44; while new estimates report 1 case per 100 children and adolescents&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Early diagnosis in a patient with PDD is particularly difficult&#46; However&#44; when a complete neurological screening is performed in the first year of life&#44; doctors can identify 40&#37; of all children with a PDD&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#8211;17</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In this study&#44; we describe the main neurological manifestations and age of diagnosis in 393 patients with different types of PDDs&#46; We also analysed the yearly number of new cases at a centre specialising in care for children with neurological problems&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Subjects</span><p id="par0035" class="elsevierStylePara elsevierViewall">We reviewed all consecutive files pertaining to patients diagnosed with a PDD and examined in CENNA&#44; the neurological centre for children and adolescents in Monterrey &#40;Nuevo Le&#243;n&#41; Mexico&#44; between 1968 and 2009&#46; We included all cases with at least 1 consultation with a specialist in paediatric neurology and a neuropsychological assessment confirming the diagnosis of PDD&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">For cases recorded between 1980 and 1987&#44; we applied DSM-III diagnostic criteria&#59; for cases from 1987 to 1994&#44; DSM-III-R&#59; for cases from 1994 to 2000&#44; DSM-IV criteria&#59; and after 2000&#44; DSM-IV-TR criteria&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Assessments</span><p id="par0045" class="elsevierStylePara elsevierViewall">We began by listing the reasons why cases had been referred to our centre and recorded patients&#8217; medical histories&#44; age&#44; sex&#44; and the results of different neurological assessments&#46; Reasons for referral were defined as follows&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Speech impairments&#59; language problems affecting either verbal communication &#40;echolalia&#44; prosodic abnormality&#44; incomprehensible language&#44; low vocabulary for the child&#39;s age&#44; inability to begin or follow a conversation&#41; or non-verbal communication &#40;problems with body language&#44; taking turns&#44; and understanding sarcasm or jokes&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Language regression&#59; progressive language loss&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Complete lack of language or speech&#44; or use of incomprehensible sounds&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Socialisation problems&#44; including cases of avoiding eye contact&#44; problems developing interpersonal relationships&#44; no desire to display or share interests&#44; and poor expression of emotions&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">e&#46;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Behaviour problems&#58; harm to self or others&#44; uneasiness&#44; or lack of obedience&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">f&#46;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Learning problems such as poor performance at school and difficulties with reading&#44; writing&#44; or mathematics&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">g&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Stereotyped behaviours&#44; whether motor &#40;flapping&#44; swaying&#44; or running in circles&#41; or verbal &#40;repeating words&#44; phrases&#44; or songs&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">h&#46;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Psychomotor delay&#59; delay in motor or psychosocial abilities identified with or without the use of standardised tests of any type&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">i&#46;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Convulsions of any type&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">j&#46;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Deafness&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">k&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Suspected PDD&#46;</p></li></ul></p><p id="par0105" class="elsevierStylePara elsevierViewall">The neuropsychological evaluation included an intelligence quotient &#40;IQ&#41; measurement using the Minnesota intelligence scale for children aged 18 months to 6 years&#59; the Wechsler Preschool and Primary Scale of Intelligence &#40;WPPSI&#41; for children aged 3 years and 10 months to 6 years and 7 months&#59; and the Wechsler Intelligence Scale for Children&#44; revised edition &#40;WISC-R&#41; for children aged 6 to 16 years&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The diagnostic criteria for PDD were established based on the Childhood Autism Rating Scale &#40;CARS&#44; 1966&#41;&#44; the Autism Spectrum Screening Questionnaire &#40;ASSQ&#44; 1981&#41; by Lorna Wing&#44; and the CENNA inventory of characteristics of autistic children &#40;ICCAN-R&#44; 1992&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">We used Schopler and Reichler&#39;s psychoeducational profile &#40;PEP&#44; 1972&#41; to evaluate memory&#44; language&#44; visuospatial and visuoperceptual abilities&#44; and fine and gross motor skills&#46; Lastly&#44; we used the Vineland Social Maturity Scale &#40;1984&#41; to measure children&#39;s level of social adaptation&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">We also analysed the age at which the child first came to the centre and the number of new cases per year&#46; Statistical analysis was performed using the Excel<span class="elsevierStyleSup">&#174;</span> program by Microsoft<span class="elsevierStyleSup">&#174;</span> and predictive analytic software SPSS<span class="elsevierStyleSup">&#174;</span> version 18 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#41;&#46; Data with a continuous distribution were expressed as means and standard deviations&#46; Some categorical variables were contrasted using the chi-square test&#44; or by using the <span class="elsevierStyleItalic">t</span>-test and analysis of variance &#40;ANOVA&#41; when examining more than 2 variables with a normal distribution&#46; Binary logistic regression analysis was performed with presence or absence of each of the autism spectrum disorders as the dependent variable in order to detect any potentially significant associations with age at detection&#44; sex&#44; neuropsychological tests&#44; or anomalies in the electroencephalogram &#40;EEG&#41;&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0125" class="elsevierStylePara elsevierViewall">We completed a retrospective and descriptive study of a series of 393 cases&#46; In this study&#44; we obtained data from the files of patients diagnosed with PDD according to the tools that were available at the time of diagnosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Classification of PDD</span><p id="par0130" class="elsevierStylePara elsevierViewall">The most frequent category was autism&#44; which accounted for 82&#46;1&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>323&#41; of cases in the series&#44; including 15 cases that were diagnosed before PDD was divided into categories&#46; The next most common category &#40;9&#46;9&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#41; was PDD-NOS&#59; Asperger syndrome accounted for 4&#46;8&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;&#44; and Rett syndrome&#44; 3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&#46; There were no diagnoses of childhood disintegrative disorder&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">PDD was diagnosed in 6 patients using criteria predating DSM-III&#59; in 9 patients using DSM-III criteria&#59; in 62 patients using DSM-III-R criteria&#59; in 160 using DSM-IV&#59; and in 156 using DSM-IV-TR&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Frequency of new cases per year</span><p id="par0140" class="elsevierStylePara elsevierViewall">The number of new cases per year is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; One of our goals was to determine whether or not age at the time of detection of PDD has decreased&#46; However&#44; the mean age at which autism spectrum disorders are identified did not vary with respect to the chronological year when we compared all of the mean ages at detection for each year using ANOVA &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;13&#41;&#46; The analysis was performed by dividing the sample into 10-year periods and 2 groups corresponding to before and after use of DSM-IV criteria&#59; the mean and significance level remained the same&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Reasons for referral</span><p id="par0145" class="elsevierStylePara elsevierViewall">The most common reasons for referral throughout the study population were language problems &#40;absence&#44; disorders&#44; or regression of language&#41;&#44; found in 58&#46;7&#37; of the cases&#44; followed by behavioural problems in 16&#46;2&#37; of cases and socialisation problems in 7&#46;6&#37;&#46; In 62&#46;5&#37; of the autism cases&#44; the initial symptom was language disorder&#44; whereas the initial symptom was behavioural and socialisation disorder in 68&#46;4&#37; of the cases of Asperger syndrome&#46; Patients with Rett syndrome were most frequently referred due to psychomotor delays &#40;41&#46;7&#37;&#41; and language regression &#40;25&#37;&#41;&#59; these 2 motives for concern accounted for 8 of the 12 patients&#46; Reasons for referral are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> &#40;neuropsychological evaluations&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Intelligence quotient was measured in 309 autistic patients&#59; scores of 69 or less were found in 227&#44; meaning that intellectual disability was present in 73&#46;5&#37; &#40;95&#37; confidence interval&#44; 68&#46;5&#37;&#8211;78&#46;4&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; None of the patients with Asperger syndrome had intellectual disability and their mean IQ score was 103 &#40;range&#44; 77&#8211;118&#41;&#46; All patients with Rett syndrome had moderate to severe intellectual disability&#46; Intellectual disability was also present in 46&#46;9&#37; of the patients with PDD-NOS &#40;95&#37; confidence interval&#44; 31&#46;2&#8211;62&#46;5&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Distribution by sex and age</span><p id="par0155" class="elsevierStylePara elsevierViewall">Ages at which PDD was detected ranged from 4 months to 15 years&#44; with a mean of 4&#46;4 years&#46; The mean age in the autistic patient group was 4&#46;1 &#40;&#177;2&#46;15&#41; years&#46; All patients with Asperger syndrome were male&#44; and their mean age at diagnosis was 8 years &#40;&#177;3&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; As would be expected&#44; all 12 patients with Rett syndrome were female&#46; Age at detection and sex distribution were significantly different in this category &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; compared to other categories in the autism spectrum&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Other neurological findings</span><p id="par0160" class="elsevierStylePara elsevierViewall">In 4&#46;5&#37; of cases&#44; patients were referred due to experiencing seizures and were later diagnosed with a PDD&#46; EEG was performed on 78 of the 393 patients &#40;19&#46;8&#37;&#41;&#59; 37 EEGs &#40;47&#46;4&#37;&#41; revealed an anomaly&#46; Other diseases in addition to the autism spectrum disorder were diagnosed in 3&#46;8&#37; of cases&#46; These included 7 cases of idiopathic epilepsy&#44; 3 cases of tuberous sclerosis&#44; 2 cases of Lennox&#8211;Gastaut syndrome&#44; 1 of hypomelanosis of Ito&#44; and 1 of microcephaly&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">Our study is one of the first to analyse the distribution of patients with autistic traits&#46; It supports existing literature in that it finds classical forms of autism to be predominant&#44; while other categories&#44; such as Asperger or Rett syndrome&#44; account for less than 10&#37; of the total cases&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In recent decades&#44; there has been an increase in the number of children diagnosed with PDD&#46; This increase appears to be linked to better knowledge of the symptoms of the disorder and the development of new diagnostic tools&#46; The gold standard evaluations for diagnosing PDD are DSM-IV&#44; the autism diagnostic observation schedule &#40;ADOS&#41;&#44; and the revised autism diagnostic interview &#40;ADI-R&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The increase in PDD prevalence is a controversial topic worldwide&#46; Various theories have been used to try to explain this phenomenon&#44; including the shift toward the concept of the &#8216;autism spectrum&#8217; rather than the concept of a single entity&#46; This accounts for there being more patients with PDD&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Increased knowledge of autism among the general population may lead to parents&#44; family members or health professionals suspecting such a disorder in young children&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The current study was carried out in a paediatric neurology centre of reference in northern Mexico&#44; and shows that a significant number of patients have been diagnosed with a PDD in recent decades&#46; However&#44; the prevalence of autism in Mexico is unknown&#46; The strategy for measuring it could involve using a national system of records capable of demonstrating changes in the prevalence of this disorder in an epidemiologically valid way&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Howlin et al&#46; report that mean age of diagnosis in developed countries has dropped from 6&#46;8 years to 2&#46;7 years<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#59; our study shows a mean age of 4 years at referral and diagnosis&#46; Most of the patients suffer from lifelong disability which affects them directly and also has an impact on the dynamic of their families&#46; Although evidence is limited in this area&#44; the general consensus is that early intervention in PDD cases can improve multiple areas of the patient&#39;s quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Casuistics are somewhat heterogeneous owing to the long time period spanned by the study&#46; Conclusions regarding increases in the number of diagnoses were not easy to analyse due to diagnostic criteria having changed during the study period&#46; This is also problematic when we make comparisons to determine whether disorders are being diagnosed earlier&#46; Even when groups are divided up by decades&#44; half-decades&#44; or by diagnosis before or after publication of DSM-IV criteria&#44; the mean age at diagnosis remains approximately 4 years&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">One relevant finding from our study is that language disorders were the initial symptoms of autism in 50&#37;&#8211;60&#37; of the cases&#46; This figure is lower than the 80&#37; reported by Tuchman et al&#46; as the percentage of parents who observe language development problems in their autistic children&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> It is possible that language problems being detected later by both parents and primary care doctors would have contributed to the children in that series being diagnosed when they were older&#46; We should also note that language disorders are not limited to patients with PDD&#46; They may be associated with intellectual disability&#44; or be classified as developmental or specific language disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Differential diagnosis is clinical&#44; and it confirms the presence of abnormalities in other cognitive and behavioural areas that would be typical of PDD&#46; Performing a neuropsychological evaluation is extremely important if there are any doubts about the diagnosis&#46; It also provides information about the patient&#39;s cognitive abilities&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Our study highlights the need for longitudinal studies that evaluate how diagnosing a patient before age 2 may affect the patient&#39;s quality of life&#46; Checking developmental milestones was only added to Mexico&#39;s guidelines for childhood disease prevention and management<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> a decade ago&#46; However&#44; it is clear that we need to develop more suitable screening methods for autism spectrum disorders and include them in the guidelines&#46; This will enable the paediatrician&#44; family doctor&#44; nursing staff&#44; and any other professionals in charge of well-child care to recognise signs of PDD and diagnose them as early as possible so that the child can come under the care of a multidisciplinary group of experts&#46; The primary care doctor must be able to recognise suspicious behaviour or signs in order to begin the process of diagnosing and then treating the condition&#46; Recent studies suggest that clinical signs that may point to autism in children younger than 2 years include absence of response when called by name&#44; lack of reciprocal play&#44; lack of motor imitation &#40;does not copy the motor movements of others&#41;&#44; problems interacting with others &#40;does not point fingers or try to attract another person&#39;s attention&#41;&#44; and responding with gestures&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;25</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Psychomotor development problems are common in patients with PDDs&#46; Identifying such problems in patients will have important repercussions for making decisions regarding treatment&#46; We found intellectual disability in 73&#46;5&#37; of the cases&#44; a similar percentage to that reported by other authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> This demonstrates the need to rule out PDD in patients initially diagnosed with mental retardation&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The prevalence of epilepsy in PDD patients ranges from 6&#37; to 38&#37; according to some authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#8211;30</span></a> Certain forms of epilepsy such as Landau&#8211;Kleffner syndrome&#44; West syndrome and continuous spikes and waves during slow sleep are associated with PDD&#46; This is why EEGs should be performed&#44; especially in patients displaying neurological regression&#46; We must thoroughly evaluate any cases that might benefit from anticonvulsants&#44; since the frequency of abnormal EEG readings in patients with PDD and no clinical signs of seizures is about 45&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> In our series&#44; 78 patients had an EEG and 47&#46;4&#37; of those cases had abnormal EEG readings&#46; This was somewhat higher than the rate reported in the literature&#59; also&#44; 4&#46;5&#37; were epileptic&#46; Recent evidence shows that all patients with autism are likely to present abnormal EEG findings when they are analysed under certain conditions&#46; These include poorer integration of the anterior&#8211;posterior plane than would be expected at the child&#39;s age&#44; and increased neural noise caused by hyperexcitability of the primary somatosensory cortex&#46; The latter may be related to the severity of symptoms of the disorder&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Although this is a retrospective study based on data from medical records with a moderate selection bias due to the type of institution&#44; we believe it provides important information about the distribution of the different autism spectrum disorders&#44; the age at which the disorder begins to be noticed by parents as a medical problem&#44; and the main symptoms which cause parents to seek care in specialised centres&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In defining PDDs as developmental disorders of the brain that may arise during the prenatal stage due to neuronal network dysfunction&#44; we are considering a number of different causes&#44; such as alterations in the cellular architecture of the central nervous system and&#47;or neurotransmitters&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#44;34</span></a> The most relevant task in current research on autism is searching for aetiological and&#47;or risk factors which&#44; in the near future&#44; will enable us to opt for specific molecular treatments for a disease which is currently severe&#44; disabling&#44; and incurable&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">In the past decade&#44; available studies have shown that a wide variety of genetic mechanisms are involved in the aetiology of PDDs&#46; Examples include monogenic disorders such as Rett syndrome&#59; microdeletion or microduplication syndromes&#59; anomalous imprinting&#59; variations in the number of copies&#59; and polymorphisms susceptible to the disorder&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The autistic behavioural phenotype has been found in more than 100 genetic syndromes&#44; including fragile X syndrome and tuberous sclerosis&#46; Based on these findings&#44; it is now proposed that PDDs be categorised as syndromic or non-syndromic&#46; Even in non-syndromic cases&#44; scientists have identified changes in the sequence or function of various genes&#44; including <span class="elsevierStyleItalic">NLGN3</span>&#44; <span class="elsevierStyleItalic">NLGN4</span>&#44; <span class="elsevierStyleItalic">PTEN</span>&#44; <span class="elsevierStyleItalic">SHANK</span>&#44; etc&#46; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#44;36</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0225" class="elsevierStylePara elsevierViewall">The syndromic component of autism may be found in up to 40&#37; of cases when diagnostic methods such as microarray-based comparative genomic hybridisation are used to identify small losses or gains in genetic material&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">The cases in our study include 5 patients with hereditary diseases&#44; highlighting the importance of genetic evaluation in cases with PDD&#46; Recent guidelines for studying the genetic causes of PDDs are available&#46; The American College of Medical Genetics published its recommendations in 2008&#44; and the American Academy of Pediatrics published its own statement in 2010&#46; Since they are so recent&#44; these recommendations were not completely integrated in our study cases&#46; Despite the fact that genetic studies are being developed and made available in many areas of the world&#44; many countries&#44; including Mexico&#44; face both technological and economic barriers that prevent their routine use&#46; In fact&#44; the capacity to study the genetic causes of autism is even limited in highly specialised neurology centres&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#44;39</span></a> Our group decided to evaluate each PDD case in order to determine what type of study to request&#44; rather than subjecting patients to full diagnostic panels that most of those treated in our centre would be unable to afford&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">PDDs are frequently seen in neurology centres&#46; The aetiological perception of these entities has changed&#44; and so have our means of diagnosing and treating them&#46; The solution to providing total care for children with PDDs is twofold&#46; In addition to promoting training for health professionals so as to improve their diagnostic accuracy&#44; we also need infrastructure and staff trained to provide specialised care using the best resources at their disposal&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "identificador" => "xres169981"
          "titulo" => array:5 [
            0 => "Abstract"
            1 => "Introduction"
            2 => "Patients and methods"
            3 => "Results"
            4 => "Conclusions"
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        ]
        1 => array:2 [
          "identificador" => "xpalclavsec158056"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres169982"
          "titulo" => array:5 [
            0 => "Resumen"
            1 => "Introducci&#243;n"
            2 => "Pacientes y m&#233;todos"
            3 => "Resultados"
            4 => "Conclusiones"
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec158055"
          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Patients and methods"
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            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Subjects"
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            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Assessments"
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          ]
        ]
        6 => array:3 [
          "identificador" => "sec0025"
          "titulo" => "Results"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Classification of PDD"
            ]
            1 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Frequency of new cases per year"
            ]
            2 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Reasons for referral"
            ]
            3 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Distribution by sex and age"
            ]
            4 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Other neurological findings"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conflicts of interest"
        ]
        9 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2011-06-14"
    "fechaAceptado" => "2011-09-11"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec158056"
          "palabras" => array:6 [
            0 => "Autism spectrum disorders"
            1 => "Language disorders"
            2 => "Autism"
            3 => "Neurodevelopmental delay"
            4 => "Early detection"
            5 => "Epidemiological data"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec158055"
          "palabras" => array:6 [
            0 => "Trastornos del espectro autista"
            1 => "Problemas de lenguaje"
            2 => "Autismo"
            3 => "Trastornos del neurodesarrollo"
            4 => "Detecci&#243;n temprana"
            5 => "Aspectos epidemiol&#243;gicos"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The autism spectrum disorders are group of conditions characterised by qualitative impairments in social communication&#59; in the interaction and imagination&#59; with a restricted range of interests and stereotyped repetitive behaviours&#46; Frequently&#44; there is a delay in the age of detection&#44; and therefore in starting multidisciplinary evaluations and interventions&#44; which may result in a worst prognosis and an impaired quality of life for both children and parents&#46; The aim of our study was to describe some clinical and epidemiological data including the age of detection and main initial complaints present in children with autism disorders from a paediatric neurology centre&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 393 medical records of consecutive cases with a diagnosis of autism spectrum disorders were reviewed&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Autism was diagnosed in 82&#46;1&#37; of the cases&#44; unspecified pervasive disorder in 9&#46;9&#37;&#44; and Asperger syndrome in 4&#46;8&#37;&#46; Sixty percent of autistic children presented with a language disorder as their main complaint&#46; The average age of detection was 4 years&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Compared with other countries&#44; age of detection is delayed&#46; A Primary Care based screening and surveillance are required in order to improve prognosis and quality of life of children with an Autism Spectrum Disorder&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los trastornos del espectro autista son un grupo de des&#243;rdenes que se caracterizan por problemas en la socializaci&#243;n&#44; en la comunicaci&#243;n verbal y no verbal&#59; y por patrones de conducta repetitivos e intereses restringidos&#46; La edad en la que se identifican var&#237;a seg&#250;n sea la intensidad e instalaci&#243;n de los s&#237;ntomas iniciales del padecimiento&#46; En las mejores condiciones de atenci&#243;n&#44; las primeras manifestaciones se notan alrededor de los doce meses de edad y el diagn&#243;stico se define entre los dos y tres a&#241;os&#46; Con frecuencia la b&#250;squeda de atenci&#243;n m&#233;dica y el inicio de las intervenciones se retrasan por la dificultad en la identificaci&#243;n de signos incipientes del trastorno&#46; Los objetivos de nuestro estudio fueron describir las manifestaciones cl&#237;nicas iniciales y aspectos epidemiol&#243;gicos en pacientes con sospecha diagn&#243;stica de espectro autista referidos a un centro neuropedi&#225;trico&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; an&#225;lisis sistem&#225;tico retrospectivo de 393 expedientes consecutivos con alg&#250;n trastorno del espectro autista&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Entre los casos revisados 82&#44;1&#37; correspondieron al diagn&#243;stico de autismo&#44; 9&#44;9&#37; trastorno inespec&#237;fico&#44; 4&#44;8&#37; Asperger y 3&#37; con s&#237;ndrome de Rett&#46; El promedio de edad a su primera evaluaci&#243;n fue de 4&#44;4 a&#241;os&#46; El 62&#44;5&#37; de los casos con autismo fueron detectados por problemas de lenguaje&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La edad de diagn&#243;stico comparada con otros pa&#237;ses sigue siendo tard&#237;a&#46; Es necesario favorecer la detecci&#243;n temprana para mejorar el pron&#243;stico y la calidad de vida de los ni&#241;os con trastorno del espectro autista&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Bravo Oro A&#46; et al&#46; Manifestaciones iniciales de los trastornos del espectro autista&#46; Experiencia en 393 casos atendidos en un centro neurol&#243;gico infantil&#46; Neurolog&#237;a&#46; 2012&#59;27&#58;414&#8211;20&#46;</p>"
      ]
    ]
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Number of new cases of autism spectrum disorders per year&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Autism &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>323&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Asperger syndrome &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Rett syndrome &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">PDD-NOS &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age in years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;1 &#40;&#177;2&#46;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;&#177;3&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;6 &#40;&#177;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;3 &#40;&#177;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female patients &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53 &#40;16&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intelligence quotient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">61 &#40;&#177;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">103 &#40;&#177;13&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">N&#46;A&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">73 &#40;&#177;20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">15 &#40;46&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara">Mean age and intellectual coefficient were significantly higher in cases with Asperger syndrome than in cases of other autism spectrum disorders&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Characteristics of pervasive developmental disorders&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Reasons for referral&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Autism &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>323&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Asperger syndrome &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Rett syndrome &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">PDD-NOS &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lack of language &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82 &#40;25&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2 &#40;16&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;15&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Language difficulties&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88 &#40;27&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;21&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;30&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Language regression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;9&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Socialisation problems&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;6&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;36&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Behavioural disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;15&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;31&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;23&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Learning disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;2&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;10&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stereotyped behaviours&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;2&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psychomotor retardation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;4&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;41&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Seizures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;3&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;16&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;12&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hearing loss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;0&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Referral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab264942.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Reasons for referral&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Gene &#40;OMIM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Locus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Clinical phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NLGN3 &#40;<span class="elsevierStyleInterRef" href="omim:300336">300336</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neuroligin-3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Xq28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Synapse formation and function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autism&#44; Asperger&#44; PDD-NOS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NLGN4 &#40;<span class="elsevierStyleInterRef" href="omim:300427">300427</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neuroligin-4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Xp22&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Synapse formation and function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autism&#44; Asperger&#44; PDD-NOS&#44; X-linked intellectual disability&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NRXN1 &#40;<span class="elsevierStyleInterRef" href="omim:600565">600565</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neurexin-1&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2p16&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Associated with neuroligins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autism with seizures and facial dysmorphism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SHANK3 &#40;<span class="elsevierStyleInterRef" href="omim:606230">606230</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SH3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22q13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postsynaptic organisation and neuroligin binding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autism with severe language and socialisation deficiencies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HOXA1 &#40;<span class="elsevierStyleInterRef" href="omim:142955">142955</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Homeobox Protein Hox A1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17p15&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Essential factor for head and neck growth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PTEN &#40;<span class="elsevierStyleInterRef" href="omim:601728">601728</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Phosphatidylinositol&#40;3&#44;4&#44;5&#41;-triphosphate 3-phosphatase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10q23&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Absence causes increase in dendrites and axonal growth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDD with macrocephaly&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">mEcP2 &#40;<span class="elsevierStyleInterRef" href="omim:300005">300005</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Methyl-CpG binding domain protein 2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Xq28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Located in promoters and other proteins associated with chromatin repression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autism&#44; Rett syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RELN &#40;<span class="elsevierStyleInterRef" href="omim:600514">600514</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reelin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7q22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Marker of neuronal migration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autism and schizophrenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UBE3A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ubiquitin-protein ligase E3A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15q11&#8211;q13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regulation of neuronal activation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDD and Angelman syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Genes involved in non-syndromic autism&#46;</p>"
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      "titulo" => "References"
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                      "Revista" => array:6 [
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                      "titulo" => "Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames&#58; the Special Needs and Autism Project &#40;SNAP&#41;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
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                      "doi" => "10.1016/S0140-6736(06)69041-7"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Prevalence of autism spectrum disorders &#8211; Autism and Developmental Disabilities Monitoring Network&#44; United States"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
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                  "host" => array:1 [
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                      "Revista" => array:6 [
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                        "paginaFinal" => "20"
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                  "contribucion" => array:1 [
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                            0 => "J&#46;S&#46; Nicholas"
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Article information

ISSN: 21735808
Original language: English

DOI:10.1016/j.nrleng.2011.09.002

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	4	1	5
2024 October	27	9	36
2024 September	38	8	46
2024 August	30	7	37
2024 July	45	7	52
2024 June	25	2	27
2024 May	30	6	36
2024 April	20	15	35
2024 March	60	12	72
2024 February	52	15	67
2024 January	58	4	62
2023 December	48	11	59
2023 November	59	19	78
2023 October	59	17	76
2023 September	38	5	43
2023 August	42	14	56
2023 July	29	12	41
2023 June	45	4	49
2023 May	58	7	65
2023 April	55	10	65
2023 March	46	7	53
2023 February	31	8	39
2023 January	19	7	26
2022 December	28	7	35
2022 November	29	10	39
2022 October	28	7	35
2022 September	18	19	37
2022 August	27	11	38
2022 July	26	9	35
2022 June	17	10	27
2022 May	41	10	51
2022 April	52	18	70
2022 March	69	9	78
2022 February	36	9	45
2022 January	62	12	74
2021 December	56	4	60
2021 November	38	16	54
2021 October	50	9	59
2021 September	54	6	60
2021 August	62	9	71
2021 July	23	11	34
2021 June	22	13	35
2021 May	24	7	31
2021 April	69	17	86
2021 March	45	12	57
2021 February	45	8	53
2021 January	25	9	34
2020 December	24	6	30
2020 November	30	6	36
2020 October	26	9	35
2020 September	21	8	29
2020 August	34	12	46
2020 July	40	15	55
2020 June	27	3	30
2020 May	22	13	35
2020 April	23	4	27
2020 March	32	7	39
2020 February	35	5	40
2020 January	37	3	40
2019 December	33	4	37
2019 November	24	8	32
2019 October	21	7	28
2019 September	18	4	22
2019 August	5	4	9
2019 July	24	12	36
2019 June	37	8	45
2019 May	102	8	110
2019 April	16	17	33
2019 March	12	7	19
2019 February	11	7	18
2019 January	7	3	10
2018 December	8	7	15
2018 November	14	1	15
2018 October	5	8	13
2018 September	6	3	9
2018 August	4	2	6
2018 July	6	3	9
2018 June	4	1	5
2018 May	9	3	12
2018 April	7	1	8
2018 March	4	2	6
2018 February	4	4	8
2018 January	11	3	14
2017 December	22	1	23
2017 November	7	2	9
2017 October	11	4	15
2017 September	18	3	21
2017 August	13	4	17
2017 July	14	1	15
2017 June	15	16	31
2017 May	16	8	24
2017 April	6	2	8
2017 March	9	23	32
2017 February	8	2	10
2017 January	13	3	16
2016 December	23	4	27
2016 November	16	3	19
2016 October	25	6	31
2016 September	17	5	22
2016 August	13	4	17
2016 July	25	1	26
2016 June	25	14	39
2016 May	24	9	33
2016 April	17	7	24
2016 March	36	13	49
2016 February	23	9	32
2016 January	15	2	17
2015 December	22	8	30
2015 November	11	2	13
2015 October	23	8	31
2015 September	20	2	22
2015 August	15	4	19
2015 July	16	8	24
2015 June	10	3	13
2015 May	14	3	17
2015 April	21	11	32
2015 March	18	4	22
2015 February	17	2	19
2015 January	33	8	41
2014 December	47	9	56
2014 November	26	5	31
2014 October	25	6	31
2014 September	24	6	30
2014 August	27	6	33
2014 July	24	6	30
2014 June	15	5	20
2014 May	21	10	31
2014 April	17	7	24
2014 March	25	6	31
2014 February	16	5	21
2014 January	17	8	25
2013 December	31	7	38
2013 November	28	7	35
2013 October	40	9	49
2013 September	37	7	44
2013 August	44	8	52
2013 July	22	2	24

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