Letter to the Editor
Jansen-de Vries syndrome. First case diagnosed in Spain
Síndrome de Jansen-de Vries. Primer caso diagnosticado en España
Read
8195
Timeswas read the article
776
Total PDF
7419
Total HTML
Share statistics
array:25 [ "pii" => "S2173580821000262" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2020.06.005" "estado" => "S300" "fechaPublicacion" => "2021-05-01" "aid" => "1444" "copyright" => "Sociedad Española de Neurología" "copyrightAnyo" => "2020" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:330-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:20 [ "pii" => "S0213485320301997" "issn" => "02134853" "doi" => "10.1016/j.nrl.2020.06.006" "estado" => "S300" "fechaPublicacion" => "2021-05-01" "aid" => "1444" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:330-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Editor</span>" "titulo" => "Síndrome de Jansen-de Vries. Primer caso diagnosticado en España" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "330" "paginaFinal" => "332" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Jansen-de Vries syndrome. First case diagnosed in Spain" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1194 "Ancho" => 905 "Tamanyo" => 164010 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fenotipo del paciente a la edad de 7 años. Frente amplia, pabellones auriculares de implantación baja, amplios y rotados posteriormente (se objetiva el derecho en la foto), leve hipotelorismo, epicanto bilateral de predominio izquierdo, nariz bulbosa con narinas pequeñas, filtro liso, labio superior fino e inferior grueso y boca grande.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Martín Fernández-Mayoralas, A.L. Fernández-Perrone, A. Jiménez de Domingo, A. Alba Menéndez, A. Fernández-Jaén" "autores" => array:5 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Martín Fernández-Mayoralas" ] 1 => array:2 [ "nombre" => "A.L." "apellidos" => "Fernández-Perrone" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Jiménez de Domingo" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Alba Menéndez" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Fernández-Jaén" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173580821000262" "doi" => "10.1016/j.nrleng.2020.06.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821000262?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485320301997?idApp=UINPBA00004N" "url" => "/02134853/0000003600000004/v1_202104210950/S0213485320301997/v1_202104210950/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2173580821000316" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2020.06.009" "estado" => "S300" "fechaPublicacion" => "2021-05-01" "aid" => "1463" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:332-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Sweating as a presentation of focal epilepsy: clinical case report" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "332" "paginaFinal" => "334" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Sudoración como presentación de epilepsia focal: descripción de un caso clínico" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 1422 "Ancho" => 1583 "Tamanyo" => 186775 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Sweating in the patient's right lower limb during an epileptic seizure.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. López-Bravo, A.A. Sanabria-Sanchinel, M. Marín-Gracia, A. Viloria-Alebesque" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "López-Bravo" ] 1 => array:2 [ "nombre" => "A.A." "apellidos" => "Sanabria-Sanchinel" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Marín-Gracia" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Viloria-Alebesque" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485320302231" "doi" => "10.1016/j.nrl.2020.06.013" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485320302231?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821000316?idApp=UINPBA00004N" "url" => "/21735808/0000003600000004/v1_202105110731/S2173580821000316/v1_202105110731/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2173580821000274" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2020.06.006" "estado" => "S300" "fechaPublicacion" => "2021-05-01" "aid" => "1445" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:329-30" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "HHV-6 meningoencephalitis in an immunocompetent patient with influenza virus co-infection" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "329" "paginaFinal" => "330" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Meningoencefalitis por HHV-6 en un paciente inmunocompetente asociado a coinfección por virus de la gripe" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "R. Jiménez Bolaños, A. Díaz Díaz, I. Sánchez-Miranda Román, J.P. Castellano Santana" "autores" => array:4 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "Jiménez Bolaños" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Díaz Díaz" ] 2 => array:2 [ "nombre" => "I." "apellidos" => "Sánchez-Miranda Román" ] 3 => array:2 [ "nombre" => "J.P." "apellidos" => "Castellano Santana" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485320302000" "doi" => "10.1016/j.nrl.2020.06.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485320302000?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821000274?idApp=UINPBA00004N" "url" => "/21735808/0000003600000004/v1_202105110731/S2173580821000274/v1_202105110731/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Jansen-de Vries syndrome. First case diagnosed in Spain" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "330" "paginaFinal" => "332" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "D. Martín Fernández-Mayoralas, A.L. Fernández-Perrone, A. Jiménez De Domingo, A. Alba Menéndez, A. Fernández-Jaén" "autores" => array:5 [ 0 => array:4 [ "nombre" => "D." "apellidos" => "Martín Fernández-Mayoralas" "email" => array:1 [ 0 => "daniel.martinf@quironsalud.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:4 [ "nombre" => "A.L." "apellidos" => "Fernández-Perrone" "email" => array:1 [ 0 => "afernandezj@quironsalud.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Jiménez De Domingo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Alba Menéndez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "Fernández-Jaén" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Neuropediatría, Hospital Universitario Quirónsalud, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Genómica y Medicina, Instituto de Estudios Celulares y Moleculares, Lugo, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Facultad de Medicina, Universidad Europea de Madrid, Villaviciosa de Odón, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de Jansen-de Vries. Primer caso diagnosticado en España" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 689 "Ancho" => 905 "Tamanyo" => 136982 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Small hands with brachydactyly (especially in distal phalanxes) and clinodactyly.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Jansen-de Vries syndrome (JDVS: MIM#617450), also known as “intellectual developmental disorder with gastrointestinal difficulties and high pain threshold (IDDGIP),” is an autosomal dominant disease<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> described in at least 20 patients<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>; to our knowledge, the patient presented here is the first case to be diagnosed in Spain. In addition to its extreme rarity, its interest resides in an atypical pattern of obsessive sex drive and the absence of intellectual disability.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">PPM1D</span> gene encodes protein phosphatase Mg<span class="elsevierStyleSup">2+</span>/Mn<span class="elsevierStyleSup">2+</span> dependent 1D, a member of the PP2C family of serine/threonine protein phosphatases. The gene participates in the negative regulation of p53-dependent cellular stress.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Jansen et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> were the first to identify de novo frameshift or truncating mutations in exons 5 and 6 of <span class="elsevierStyleItalic">PPM1D</span> as the cause of a syndrome characterised by a peculiar phenotype, intellectual disability, language and behavioural impairment, gastrointestinal difficulties with cyclic vomiting,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> hypersensitivity to sound, and high pain threshold.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Our patient is an 8-year-old boy who was previously assessed due to mild psychomotor retardation (free ambulation at 2 years) and severe language and communication delay (first words at 4 years).</p><p id="par0020" class="elsevierStylePara elsevierViewall">Harmonious intrauterine growth retardation was observed during pregnancy. The child was born by vaginal delivery at 39 weeks: Apgar score: 9/10; weight: 2.175<span class="elsevierStyleHsp" style=""></span>kg (first percentile); length: 47<span class="elsevierStyleHsp" style=""></span>cm (third percentile); head circumference: 33<span class="elsevierStyleHsp" style=""></span>cm (fifth percentile). We initially observed hypotonia, feeding difficulties, gastro-oesophageal reflux disease, and constipation alternating with intermittent diarrhoea over the years.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The physical examination performed when the patient was 7 years old revealed a weight of 20.4<span class="elsevierStyleHsp" style=""></span>kg (13th percentile), height of 112<span class="elsevierStyleHsp" style=""></span>cm (second percentile), and head circumference of 48.5<span class="elsevierStyleHsp" style=""></span>cm (third percentile). We also observed subtle dysmorphic features (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The patient also presented lumbar hyperlordosis, small hands with brachydactyly (especially in the distal phalanges) and clinodactyly (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), and small feet, with bilateral nail dysplasia. Neurological examination showed no focal signs.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">His family was concerned by his sexual disinhibition, characterised by a strong desire for social relationships (despite certain difficulties adapting to his classmates) and obsessions with erotic content, associated with compulsive masturbation. He presented a high pain threshold, hypersensitivity to sound, and stereotypy of both hands at the level of the face (to release tension). These repetitive behaviours were not incapacitating, and he was able to make eye contact and showed a good level of empathy. In the neuropsychological evaluation, the WISC-V showed a total intelligence quotient of 84, with a score of 74 in working memory, the most severely impaired item. We observed pronounced attention difficulties.</p><p id="par0035" class="elsevierStylePara elsevierViewall">A bone age study revealed a delay of 2 years (–3 SD). Results of the cardiological examination, brain MRI, and EEG were normal. Further testing was performed, and whole-genome sequencing revealed heterozygous presence of a de novo frameshift mutation in exon 5 of the <span class="elsevierStyleItalic">PPM1D</span> gene (hg19; chr 17: 58734146; NM_003620.3; c.1206_1207del, p.Asn402Lysfs*31). The mutation, which was subsequently confirmed by Sanger sequencing, was not listed on any genetic database and had not previously been reported in the literature.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The most frequent physical characteristics of JDVS include hypotonia,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> delayed bone age,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> feeding difficulties and gastrointestinal problems (including vomiting and constipation),<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> and such dysmorphic features as the above-mentioned subtle facial abnormalities,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> microcephalus, hyperlordosis,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> small hands with brachyphalangia (detectable in 90% of cases), and hypoplastic nails.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> The most frequent cognitive and behavioural difficulties are speech delay,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> attention-deficit/hyperactivity disorder,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and anxiety with an obsessive-compulsive component,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> together with hyper- or hyporeactivity to sensory stimuli (hypersensitivity to sound,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> high pain threshold in 90% of cases)<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a>; many of these features are present in our patient. Hypersexuality has previously been described in patients with intellectual disability and occasionally in patients with autistic spectrum disorders.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> It is currently unclear whether this hyperactivity is part of a specific behavioural phenotype, which may have not been reported previously.</p><p id="par0045" class="elsevierStylePara elsevierViewall">We report a case of JDVS with characteristic dysmorphic features and no intellectual disability, but presenting surprising hypersexual behaviour, secondary to a novel mutation. Although disability of various degrees is considered the standard in this syndrome,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> the series by Jansen et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> includes another case with JDVS and no intellectual disability, highlighting the need for more comprehensive genetic studies in patients with complex neurodevelopmental disorders of unknown origin.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors have received no funding for this study.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Martín Fernández-Mayoralas D, Fernández-Perrone AL, Jiménez De Domingo A, Alba Menéndez A, Fernández-Jaén A. Síndrome de Jansen-de Vries. Primer caso diagnosticado en Espa˜na. Neurología. 2021;36:330–332.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1194 "Ancho" => 905 "Tamanyo" => 164010 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Phenotype of the patient at the age of 7. Wide forehead; low-set, wide ears with backward rotation (the right ear can be seen); mild hypotelorism; bilateral epicanthus, predominantly on the left; bulbous nose with small nares; smooth philtrum; thin upper lip and thick lower lip; and large mouth.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 689 "Ancho" => 905 "Tamanyo" => 136982 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Small hands with brachydactyly (especially in distal phalanxes) and clinodactyly.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel truncating variant of PPM1D penultimate exon in a Chinese patient with Jansen-de Vries syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Z. Li" 1 => "C. Du" 2 => "C. Zhang" 3 => "M. Zhang" 4 => "Y. Ying" 5 => "Y. Liang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mgg3.1120" "Revista" => array:5 [ "tituloSerie" => "Mol Genet Genomic Med" "fecha" => "2020" "volumen" => "8" "paginaInicial" => "e1120" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31916397" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "De novo truncating mutations in the last and penultimate exons of PPM1D cause an intellectual disability syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Jansen" 1 => "S. Geuer" 2 => "R. Pfundt" 3 => "R. Brough" 4 => "P. Ghongane" 5 => "J.C. Herkert" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2017.02.005" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2017" "volumen" => "100" "paginaInicial" => "650" "paginaFinal" => "658" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28343630" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Two unrelated girls with intellectual disability associated with a truncating mutation in the PPM1D penultimate exon" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Kuroda" 1 => "H. Murakami" 2 => "T. Yokoi" 3 => "T. Kumaki" 4 => "Y. Enomoto" 5 => "Y. Tsurusaki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.braindev.2019.02.007" "Revista" => array:6 [ "tituloSerie" => "Brain Dev" "fecha" => "2019" "volumen" => "41" "paginaInicial" => "538" "paginaFinal" => "541" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30795918" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel truncating PPM1D mutation in a patient with intellectual disability" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Porrmann" 1 => "A. Rump" 2 => "K. Hackmann" 3 => "N. Di Donato" 4 => "A.K. Kahlert" 5 => "J. Wagner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur J Med Genet" "fecha" => "2019" "volumen" => "62" "paginaInicial" => "70" "paginaFinal" => "72" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sexually inappropriate behaviors in seriously mentally ill children and adolescents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Adams" 1 => "J. McClellan" 2 => "D. Douglass" 3 => "C. McCurry" 4 => "M. Storck" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0145-2134(95)00015-z" "Revista" => array:6 [ "tituloSerie" => "Child Abuse Negl" "fecha" => "1995" "volumen" => "19" "paginaInicial" => "555" "paginaFinal" => "568" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7664136" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735808/0000003600000004/v1_202105110731/S2173580821000262/v1_202105110731/en/main.assets" "Apartado" => array:4 [ "identificador" => "9409" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735808/0000003600000004/v1_202105110731/S2173580821000262/v1_202105110731/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821000262?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 15 | 1 | 16 |
| 2024 October | 180 | 14 | 194 |
| 2024 September | 199 | 26 | 225 |
| 2024 August | 178 | 24 | 202 |
| 2024 July | 204 | 14 | 218 |
| 2024 June | 256 | 26 | 282 |
| 2024 May | 222 | 5 | 227 |
| 2024 April | 191 | 14 | 205 |
| 2024 March | 329 | 6 | 335 |
| 2024 February | 304 | 15 | 319 |
| 2024 January | 360 | 18 | 378 |
| 2023 December | 314 | 18 | 332 |
| 2023 November | 291 | 8 | 299 |
| 2023 October | 259 | 19 | 278 |
| 2023 September | 160 | 13 | 173 |
| 2023 August | 168 | 19 | 187 |
| 2023 July | 216 | 12 | 228 |
| 2023 June | 148 | 9 | 157 |
| 2023 May | 150 | 23 | 173 |
| 2023 April | 122 | 20 | 142 |
| 2023 March | 163 | 21 | 184 |
| 2023 February | 117 | 33 | 150 |
| 2023 January | 106 | 8 | 114 |
| 2022 December | 104 | 29 | 133 |
| 2022 November | 122 | 20 | 142 |
| 2022 October | 106 | 22 | 128 |
| 2022 September | 176 | 25 | 201 |
| 2022 August | 125 | 27 | 152 |
| 2022 July | 104 | 22 | 126 |
| 2022 June | 105 | 24 | 129 |
| 2022 May | 129 | 20 | 149 |
| 2022 April | 101 | 13 | 114 |
| 2022 March | 114 | 21 | 135 |
| 2022 February | 127 | 12 | 139 |
| 2022 January | 177 | 6 | 183 |
| 2021 December | 149 | 13 | 162 |
| 2021 November | 142 | 15 | 157 |
| 2021 October | 152 | 12 | 164 |
| 2021 September | 143 | 8 | 151 |
| 2021 August | 150 | 15 | 165 |
| 2021 July | 172 | 9 | 181 |
| 2021 June | 166 | 8 | 174 |
| 2021 May | 114 | 23 | 137 |
| 2021 April | 66 | 58 | 124 |
| 2021 March | 23 | 8 | 31 |
Show all
