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Fenotipo en pacientes con discapacidad intelectual y array-CGH patológico
Phenotype in patients with intellectual disability and pathological results in array CGH
V. Caballero Péreza,
Autor para correspondencia
vcaballero@salud.aragon.es
vicckky8@gmail.com

Autor para correspondencia.
, F.J. López Pisónb, M.D. Miramar Gallartc, A. González Álvarezd, M.C. García Jiménezb, J.P. García Iñigueze, C. Orden Ruedab, I. Gil Hernándezb, C. Fuertes Rodrigob, R. Fernando Martínezb, A. Rodríguez Vallec, M.J. Alcaine Villarroyac
a Servicio de Pediatría, Hospital Obispo Polanco, Teruel, España
b Sección de Neuropediatría, Hospital Infantil Universitario Miguel Servet, Zaragoza, España
c Sección de Genética, Hospital Universitario Miguel Servet, Zaragoza, España
d Servicio de Farmacia, Hospital Obispo Polanco, Teruel, España
e Servicio de Cuidados Intensivos Pediátricos, Hospital Infantil Universitario Miguel Servet, Zaragoza, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La discapacidad intelectual &#40;DI&#41; se caracteriza por limitaciones significativas tanto en el funcionamiento intelectual como en el adaptativo y se origina con anterioridad a los 18 a&#241;os&#46; Para los ni&#241;os menores de 5 a&#241;os se usa el t&#233;rmino retraso global del desarrollo &#40;RGD&#41; en aquellos que no cumplen los hitos esperados para su edad en las &#225;reas de desarrollo social&#44; motor o intelectual &#40;con principal relevancia del lenguaje&#41;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">1-3</span></a>&#46; Aproximadamente el 50&#37; de los casos a nivel global no tienen un diagn&#243;stico etiol&#243;gico establecido<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">4&#44;5</span></a>&#46; Las causas m&#225;s frecuentes identificadas dentro del campo de la gen&#233;tica han sido las mutaciones puntuales en genes conocidos y las alteraciones cromos&#243;micas<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; La t&#233;cnica array-comparative genomic hybridization &#40;CGH&#41; identifica tanto excesos &#40;duplicaciones&#41; como defectos &#40;deleciones&#41; de material gen&#233;tico y constituye uno de los principales test diagn&#243;sticos en ni&#241;os con trastornos del neurodesarrollo&#46; Cuando se aplica al estudio de la DI el rendimiento diagn&#243;stico var&#237;a desde un 10 a un 30&#37;&#44; seg&#250;n los criterios de selecci&#243;n de la muestra utilizados<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; El objetivo de nuestro estudio es conocer qu&#233; caracter&#237;sticas cl&#237;nicas&#44; antropom&#233;tricas y morfol&#243;gicas aparecen con mayor frecuencia en individuos afectados de DI&#47;RGD con un resultado diagn&#243;stico en la prueba del array-CGH&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><p id="par0010" class="elsevierStylePara elsevierViewall">Los criterios de selecci&#243;n de la muestra fueron&#58; <span class="elsevierStyleItalic">a&#41;</span> estar en seguimiento en la consulta de Neuropediatr&#237;a del Hospital Infantil Miguel Servet de Zaragoza&#59; <span class="elsevierStyleItalic">b&#41;</span> edad comprendida entre los 12 meses y los 18 a&#241;os&#59; <span class="elsevierStyleItalic">c&#41;</span> estar afectados de DI o RGD sin diagn&#243;stico etiol&#243;gico establecido&#44; y <span class="elsevierStyleItalic">d&#41;</span> haberse realizado la t&#233;cnica array-CGH y haber recibido el resultado antes del 1 de diciembre del 2011&#46; El n&#250;mero total de individuos que cumpl&#237;an estos criterios fue de 140&#46; El periodo de investigaci&#243;n fue de 2 a&#241;os y se desarroll&#243; por un &#250;nico investigador&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Se diagnostic&#243; de RGD a aquellos pacientes que con una edad inferior a 5 a&#241;os presentaban una alteraci&#243;n en el neurodesarrollo en 2 o m&#225;s &#225;reas seg&#250;n la escala de desarrollo Denver o Llevant&#46; Asimismo&#44; se diagnostic&#243; de DI a aquellos pacientes que a una edad igual o superior a 5 a&#241;os dispon&#237;an de un estudio de cociente intelectual<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>70&#46; En aquellos casos que no se dispon&#237;a de un estudio neuropsicol&#243;gico&#44; la DI se defini&#243; en funci&#243;n del tipo de escolarizaci&#243;n&#58; educaci&#243;n especial o con adaptaci&#243;n curricular significativa&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">M&#233;todo&#58; se envi&#243; una carta informativa de las caracter&#237;sticas del estudio a las familias y se concert&#243; una cita presencial por v&#237;a telef&#243;nica&#46; El d&#237;a de la cita se firm&#243; el consentimiento informado &#40;repetido&#41; y se registraron las principales variables demogr&#225;ficas&#44; perinatales&#44; cl&#237;nicas&#44; morfol&#243;gicas y antropom&#233;tricas de cada uno de los individuos sin conocer el resultado del test gen&#233;tico mediante entrevista cl&#237;nica y exploraci&#243;n f&#237;sica pormenorizada&#46; A posteriori&#44; se revisaron la historia cl&#237;nica y el resultado del array-CGH clasificando a los individuos en 3 grupos&#58; resultado normal&#44; resultado patol&#243;gico o resultado incierto&#46; Para llevar a cabo esta clasificaci&#243;n se consultaron las bases de datos Database of Genomic Variants &#40;DGV&#41;&#44; International Standard Cytogenomic Arrayconsortium Databases &#40;ISCA&#41;&#44; Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources &#40;DECIPHER&#41; y Online Mendelian Inheritance in Man &#40;OMIM&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">El estudio se llev&#243; a cabo siguiendo las normas deontol&#243;gicas reconocidas por la Declaraci&#243;n de Helsinki &#40;59&#46;&#170; Asamblea General&#44; Se&#250;l&#44; Corea&#44; octubre del 2008&#41;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">10</span></a>&#46; El proyecto fue revisado y aprobado por el Comit&#233; &#201;tico de Investigaci&#243;n Cl&#237;nica de Arag&#243;n&#46; Asimismo&#44; se obtuvo el consentimiento informado de cada uno de los pacientes&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">El an&#225;lisis gen&#233;tico se realiz&#243; a partir de ADN extra&#237;do de linfocitos de sangre perif&#233;rica&#44; mediante el sistema de extracci&#243;n automatizado EZ1 &#40;Quiagen GmbH&#44; Hilden&#44; Alemania&#41;&#46; Las muestras se remitieron para su an&#225;lisis mediante hibridaci&#243;n gen&#243;mica comparada sobre array a 2 laboratorios&#58; Qgenomics y Genycell Biotech&#46; La hibridaci&#243;n se llev&#243; a cabo con un microarray de 60&#46;000 sondas oligonucleot&#237;dicas&#44; repartidas por todo el genoma&#44; con mayor cobertura en regiones pericentrom&#233;ricas&#44; subtelom&#233;ricas e implicadas en trastornos gen&#243;micos recurrentes&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Una vez recogidas las variables de estudio&#44; se comprobaron la normalidad de la distribuci&#243;n con la prueba Shapiro-Wilk y la homogeneidad de varianzas mediante la prueba de Levene&#46; La asociaci&#243;n entre los factores estudiados y el resultado de la prueba array-CGH se investig&#243; mediante pruebas de contraste de hip&#243;tesis&#44; con comparaci&#243;n de proporciones cuando ambas variables eran cualitativas &#40;chi al cuadrado para variables que cumplen supuesto de normalidad y prueba exacta de Fisher cuando no la cumplen&#41; y comparaciones de medias cuando una de ellas sea cuantitativa&#44; t de Student y ANOVA para una distribuci&#243;n normal&#44; y el test de la U de Mann-Whitney para distribuciones no normales&#46; Se compar&#243; la distribuci&#243;n de las caracter&#237;sticas de los individuos con un resultado normal del array-CGH con los que presentaban un resultado patol&#243;gico&#46; Se excluy&#243; del an&#225;lisis a los individuos con un resultado incierto y el caso n&#46;&#176; 15 que simult&#225;neamente presentaba un s&#237;ndrome X fr&#225;gil y cuyas caracter&#237;sticas pod&#237;an actuar como factor de confusi&#243;n&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Para el desarrollo del modelo de regresi&#243;n log&#237;stica&#44; se procedi&#243; a un cribado de las variables explicativas&#44; a partir del an&#225;lisis de regresiones univariantes&#44; seleccionando as&#237; los potenciales factores pron&#243;sticos que se deb&#237;an incluir en el modelo multivariante &#40;valores p &#60; 0&#44;25&#41;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; Con las variables resultantes o las que por motivos cl&#237;nicos deb&#237;an estar presentes en el modelo final se exploraron los diferentes modelos multivariantes con los m&#233;todos de inclusi&#243;n y exclusi&#243;n secuencial&#44; fijando los valores p de significaci&#243;n para la inclusi&#243;n o exclusi&#243;n de variables en 0&#44;1 y 0&#44;2&#44; respectivamente&#46; En todos los casos se fij&#243; el nivel de significaci&#243;n estad&#237;stica para valores de p &#60; 0&#44;05&#46; El an&#225;lisis estad&#237;stico fue realizado mediante el programa inform&#225;tico IBM SPSS Statistics 21 &#40;SPSS Inc&#46;&#44; Chicago&#44; EE&#46; UU&#46;&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Resultados</span><p id="par0045" class="elsevierStylePara elsevierViewall">Ochenta individuos terminaron todas las fases del estudio &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Se encontraron variantes en el n&#250;mero de copias &#40;CNV&#41; en un 40&#37; de los casos y se consideraron patol&#243;gicas un 27&#44;5&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; Con respecto al tipo de desequilibrio cromos&#243;mico&#44; en un 62&#44;5&#37; de los casos se detectaron deleciones&#44; en un 6&#44;25&#37; translocaciones no equilibradas y en un 31&#44;25&#37; duplicaciones&#46; El tama&#241;o de las deleciones oscil&#243; entre 0&#44;06 y 16&#44;5 Mb y el de las duplicaciones entre 0&#44;08 y 2&#44;2 Mb&#46; En un 51&#44;6&#37; de los an&#225;lisis las alteraciones cromos&#243;micas se produjeron <span class="elsevierStyleItalic">de novo</span>&#46; En los casos heredados de un progenitor&#44; en 7 fue del padre &#40;un individuo afectado&#44; resto sanos&#41; y en 8 de la madre &#40;todas sanas&#44; aunque 2 de ellas portadoras de una translocaci&#243;n equilibrada&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Con respecto a las principales caracter&#237;sticas demogr&#225;ficas&#44; perinatales&#44; antropom&#233;tricas y cl&#237;nicas se encontr&#243; asociaci&#243;n entre los antecedentes familiares de DI y el resultado patol&#243;gico del array &#40;p &#61; 0&#44;043&#41; &#40;OR&#58; 12&#44;1&#59; IC del 95&#37;&#58; 3&#44;18-45&#44;9&#41;&#46; La media de la edad gestacional fue inferior en el grupo con array-CGH patol&#243;gico &#40;p &#61; 0&#44;006&#41;&#44; aunque no se encontraron diferencias significativas con respecto a la prematuridad en ambos grupos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Con respecto al estudio de los rasgos dism&#243;rficos cr&#225;neo-faciales se realizaron 2 comparaciones&#58; presencia o ausencia de cualquier tipo de alteraci&#243;n en cada categor&#237;a &#40;ojos&#44; orejas&#44; mand&#237;bula&#44; etc&#46;&#41; mediante test de Fisher y la comparaci&#243;n de los tipos de alteraci&#243;n encontradas en cada categor&#237;a mediante chi al cuadrado &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">A todos los niveles se encontr&#243; una mayor proporci&#243;n de rasgos dism&#243;rficos en los individuos que presentaron un test gen&#233;tico patol&#243;gico con excepci&#243;n del paladar&#46; De forma espec&#237;fica&#44; las partes en las que se encontraron alteraciones con una mayor prevalencia en el grupo con el test array-CGH alterado con nivel significativo &#40;p &#60; 0&#44;05&#41; fueron las siguientes&#58; el pelo &#40;p &#61; 0&#44;019&#41; con una mayor proporci&#243;n de pelo mal implantado &#40;OR&#58; 6&#59; IC del 95&#37;&#58; 1&#44;33-26&#44;9&#41;&#44; los labios &#40;p &#60; 0&#44;001&#41;&#44; con una mayor proporci&#243;n de labio superior fino &#40;p &#60; 0&#44;001&#41; &#40;OR&#58; 20&#44;6&#59; IC del 95&#37;&#44; 3&#44;99-109&#44;37&#41;&#59; la boca-filtrum &#40;p &#60; 0&#44;001&#41; &#40;OR&#58; 8&#44;13&#59; IC del 95&#37;&#58; 2&#44;54-25&#44;9&#41;&#44; destacando la presencia de filtrum largo &#40;p &#60; 0&#44;001&#41; y la mand&#237;bula &#40;p &#61; 0&#44;026&#41; &#40;OR&#58; 3&#44;45&#59; IC del 95&#37;&#44; 1&#44;15-10&#44;42&#41;&#44; siendo la micrognatia la caracter&#237;stica m&#225;s frecuentemente encontrada rozando la significaci&#243;n estad&#237;stica &#40;p &#61; 0&#44;065&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46; El 68&#44;4&#37; de los individuos con un array-CGH patol&#243;gico presentan m&#225;s de 3 rasgos dism&#243;rficos frente al 31&#44;2&#37; de los individuos con un resultado normal con un nivel de significaci&#243;n inferior a 0&#44;001 &#40;OR&#58; 20&#44;9&#59; IC del 95&#37;&#58; 4&#44;31-101&#44;4&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">La presencia de malformaciones cong&#233;nitas fue mayor en el grupo que present&#243; un resultado del test de array-CGH patol&#243;gico a nivel general &#40;p &#61; 0&#44;005&#41; y en los distintos subgrupos&#44; excepto a nivel digestivo&#46; El tipo de malformaci&#243;n cong&#233;nita m&#225;s frecuentemente encontrada en la muestra analizada fue a nivel del sistema nervioso central en ambos grupos &#40;donde tambi&#233;n se han incluido las alteraciones medulares&#41;&#44; seguido de las cardiacas y urogenitales pero en este caso sin diferencias significativas entre las 2s cohortes &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a> se muestran los principales rasgos dism&#243;rficos&#44; la presencia de malformaciones cong&#233;nitas y los antecedentes familiares de DI de cada uno de los casos con resultado patol&#243;gico&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">En el estudio del tono muscular se detect&#243; un predominio de la hipoton&#237;a sobre la hiperton&#237;a tanto a nivel axial como perif&#233;rico&#44; con una distribuci&#243;n similar en ambos grupos de an&#225;lisis de la hipoton&#237;a axial&#44; mientras que la proporci&#243;n de pacientes con hipoton&#237;a perif&#233;rica fue mayor en el grupo con resultado array-CGH patol&#243;gico &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabla 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">La realizaci&#243;n del estudio de regresi&#243;n log&#237;stica multivariante permiti&#243; identificar los principales factores asociados a presentar un resultado alterado de forma independiente&#44; que fueron la presencia de antecedentes familiares de DI&#44; m&#225;s de 3 rasgos dism&#243;rficos cr&#225;neo-faciales y alteraciones a nivel de los labios&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Las pruebas gen&#233;ticas que se hab&#237;an realizado previamente en el grupo del array-CGH patol&#243;gico no fueron concluyentes&#46; Se llev&#243; a cabo cariotipo en 15 individuos &#40;4 de ellos de alta resoluci&#243;n&#41; y estudio de deleciones subtelom&#233;ricas en 5 casos&#46; Se descart&#243; s&#237;ndrome X fr&#225;gil en 14 varones y 2 mujeres&#46; El caso n&#250;mero 15 merece especial atenci&#243;n&#44; ya que se descart&#243; s&#237;ndrome X fr&#225;gil en el a&#241;o 2006 por la t&#233;cnica Southern blot&#46; Ante fenotipo compatible &#40;exceptuando la microcefalia&#41;&#44; se repiti&#243; el estudio en el a&#241;o 2012&#44; presentando m&#225;s de 250 repeticiones del trinucle&#243;tido CGG mediante t&#233;cnica PT-PCR&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discusi&#243;n</span><p id="par0090" class="elsevierStylePara elsevierViewall">La t&#233;cnica de array-CGH ha supuesto un gran avance en el estudio de la DI&#47;RGD de forma que se propone como primera prueba a realizar en esta patolog&#237;a por gran parte de los autores<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">13&#44;14</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">A pesar de la limitaci&#243;n del tama&#241;o muestral&#44; es importante se&#241;alar que se ha realizado el estudio pormenorizado de las caracter&#237;sticas de forma ciega &#40;sin conocer el resultado del array-CGH&#41;&#44; por un &#250;nico investigador&#44; lo que disminuye la variabilidad y aumenta la validez interna&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">El rendimiento encontrado en nuestra muestra ha sido superior a la mayor&#237;a de las series de datos publicados que var&#237;an entre el 5 y el 25&#37;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">13&#44;14</span></a>&#46; Este hallazgo puede ser debido a los criterios de selecci&#243;n que se siguieron inicialmente a la hora de realizar el test gen&#233;tico en los que se tendi&#243; a elegir a aquellos pacientes con antecedentes familiares de DI&#44; rasgos dism&#243;rficos y&#47;o malformaciones cong&#233;nitas&#46; En aquellas series en las que se usaron criterios semejantes se han obtenido &#237;ndices de detecci&#243;n similares<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">8&#44;15</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Un 60&#37; de las alteraciones encontradas fueron deleciones&#46; Este hecho puede tener una doble explicaci&#243;n&#44; tanto t&#233;cnica como biol&#243;gica&#46; T&#233;cnicamente&#44; existe mayor probabilidad que las duplicaciones no sean detectadas&#46; Biol&#243;gicamente&#44; se ha descrito que las duplicaciones causan fenotipos menos severos y por ello se han podido perder casos en la selecci&#243;n de la muestra&#46; Tambi&#233;n se ha descrito que la frecuencia de que se produzcan duplicaciones al azar en el genoma humano es inferior a la de deleciones<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">La distribuci&#243;n de las CNV parece no ser al azar&#44; existiendo puntos calientes donde se encuentran con mayor frecuencia&#46; Estas zonas suelen ser ricas en genes y regiones con duplicaciones segmetarias<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a>&#46; En nuestra muestra&#44; la mayor&#237;a de las CNV afectan a genes implicados en la se&#241;alizaci&#243;n y la adhesi&#243;n celular&#44; o bien codifican para prote&#237;nas estructurales del sistema nervioso central<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Con respecto a la herencia&#44; los casos n&#46;&#176; 1 y 2 son secundarios a translocaciones equilibradas maternas&#46; La detecci&#243;n de translocaciones equilibradas cr&#237;pticas es extraordinariamente importante debido al alto riesgo de recurrencia&#46; Su detecci&#243;n permite el correcto asesoramiento gen&#233;tico a toda la familia&#46; En el caso 5&#44; la deleci&#243;n es heredada de su padre&#44; que presenta un grado inferior de DI que el probando&#44; lo que nos hace sospechar de la expresividad variable de la alteraci&#243;n&#46; El caso n&#46;&#176; 20 presenta una duplicaci&#243;n a nivel del cromosoma X&#44; heredada de la madre sin fenotipo reportado&#46; Esta disom&#237;a contiene genes descritos en OMIM asociados a patolog&#237;a&#46; El hecho de que la madre no presente cl&#237;nica puede ser debido al fen&#243;meno de inactivaci&#243;n selectiva del cromosoma X&#46; Por &#250;ltimo&#44; los casos n&#46;&#176; 19 y 22 son heredados de la madre sana y afectan a autosomas&#46; El caso n&#46;&#176; 19 presenta una microduplicaci&#243;n en el cromosoma 22&#44; que ha sido descrito en la literatura asociado a penetrancia incompleta y expresi&#243;n muy variable que incluye desde portadores con inteligencia normal hasta portadores con DI severa y un alto n&#250;mero de pacientes que heredan la alteraci&#243;n de un progenitor no afectado<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a>&#46; El caso n&#46;&#176; 22 presenta una duplicaci&#243;n en una zona de microduplicaciones&#47;deleciones frecuentes del cromosoma 15&#46; En la literatura cient&#237;fica existen numerosos casos en los que la duplicaci&#243;n es heredada de un progenitor con fenotipo normal&#46; Se postula que la cl&#237;nica es m&#225;s grave cuando se hereda por v&#237;a materna&#44; existiendo una gran variabilidad intrafamiliar &#40;desde inteligencia normal hasta alteraciones cognitivas graves acompa&#241;adas de epilepsia&#41;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">En las CNV clasificadas como de significado incierto&#44; las alteraciones han sido heredadas de un progenitor sano en el 90&#37; de los casos&#46; Este hecho aislado debe interpretarse de forma cautelosa&#44; ya que aunque a d&#237;a de hoy no se haya podido demostrar&#44; estos desequilibrios cromos&#243;micos pueden contribuir al fenotipo del paciente como consecuencia de la expresividad variable de los mismos&#44; efectos epigen&#233;ticos o bien debido a una mutaci&#243;n recesiva en el alelo no delecionado<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Con respecto a la antropometr&#237;a&#44; en estudios previos se ha detectado una asociaci&#243;n entre la microcefalia y el resultado patol&#243;gico del array-CGH<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a>&#46; Al calcular la proporci&#243;n de individuos con microcefalia grave &#40;per&#237;metro cef&#225;lico inferior a &#8211;3 desviaciones est&#225;ndar&#41;&#44; la proporci&#243;n es muy superior en el grupo con resultado del array-CGH patol&#243;gico aunque sin alcanzar significaci&#243;n estad&#237;stica &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; Estos hallazgos nos hacen presuponer que si nuestra muestra tuviese un n&#250;mero mayor de pacientes es probable que se reprodujesen los resultados del estudio citado con respecto a la microcefalia&#46; Otros autores han encontrado con mayor frecuencia trastornos del crecimiento en los individuos que presentaban un resultado del array-CGH patol&#243;gico&#58; Shoukier et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> refieren fallo de medro&#44; Rosell&#243; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> talla alta&#44; mientras que Vulto-van Silfhout et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a>&#44; como en el presente trabajo&#44; no encuentran asociaci&#243;n entre la evoluci&#243;n de la altura&#47;peso y el resultado del test gen&#233;tico&#46; Esta variabilidad encontrada en la literatura cient&#237;fica con respecto al crecimiento puede ser debida a los criterios de selecci&#243;n de los casos&#44; as&#237; como al resultado de la prueba de array&#44; ya que hay s&#237;ndromes que se acompa&#241;an de fallo de medro y otros de sobrecrecimiento&#46; Son necesarios estudios con un mayor n&#250;mero de individuos para determinar la implicaci&#243;n de los des&#243;rdenes de crecimiento en las alteraciones estructurales cromos&#243;micas&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Numerosos autores han publicado la asociaci&#243;n entre la presencia de alteraciones cromos&#243;micas y las malformaciones cong&#233;nitas<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">8&#44;15&#44;20</span></a>&#46; En la mayor&#237;a de las series las m&#225;s prevalentes fueron las malformaciones cardiacas y en el presente estudio fueron a nivel del sistema nervioso central&#44; principalmente las alteraciones del cuerpo calloso&#46; Este hallazgo coincide con lo publicado por Preiksaitiene et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a>&#46; Al revisar la metodolog&#237;a de los diferentes estudios&#44; se pone de manifiesto que los criterios de selecci&#243;n influyen en el tipo de malformaci&#243;n m&#225;s frecuente&#46; No obstante&#44; en nuestro estudio la distribuci&#243;n de las malformaciones fue absolutamente aleatoria&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">La presencia de rasgos dism&#243;rficos constituye una variable muy importante en nuestra muestra debido a la alta prevalencia de los mismos en los individuos afectos de DI&#47;RGD&#46; Como prueba de ello&#44; tras la exploraci&#243;n pormenorizada de los mismos&#44; solamente en un 25&#37; de los individuos con array-CGH normal y en un 13&#44;6&#37; de los casos que presentan CNV patol&#243;gicas no se detect&#243; ninguna alteraci&#243;n morfol&#243;gica menor&#46; En nuestro estudio&#44; el pelo mal implantado&#44; el filtrum largo&#44; el labio superior fino y la micrognatia fueron las caracter&#237;sticas en las que se encontraron diferencias significativas&#46; Aunque el tipo de rasgo dism&#243;rfico m&#225;s frecuente var&#237;a mucho entre unas series y otras&#44; la presencia de varios rasgos en conjunto&#44; constituye un buen indicador de la posible existencia de un desequilibrio cromos&#243;mico<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Se han publicado varios trabajos en los que se compara el rendimiento de las diferentes t&#233;cnicas diagn&#243;sticas gen&#233;ticas aplicadas al estudio de la DI&#46; Miller et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> realizaron una revisi&#243;n de 33 estudios que abarcaban 21&#46;698 pacientes y concluyeron que mientras el cariotipo de alta resoluci&#243;n ten&#237;a un rendimiento del 3&#37; &#40;excluyendo el s&#237;ndrome de Down&#41; y la aplicaci&#243;n de FISH a los tel&#243;meros un 2&#44;4&#37;&#44; la t&#233;cnica array-CGH alcanzaba un 12&#37; de diagn&#243;sticos en pacientes no seleccionados&#46; En un estudio m&#225;s reciente realizado en Europa sobre 36&#46;325 pacientes en los que se realiz&#243; cariotipo y array-CGH se detectaron CNV patol&#243;gicas en un 19&#37; de los individuos no seleccionados y solamente un 0&#44;78&#37; de las alteraciones gen&#233;ticas no hubiesen sido detectadas sin la realizaci&#243;n del cariotipo<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a>&#46; Ambos trabajos concluyen que el estudio mediante array debe ser la primera prueba en el abordaje diagn&#243;stico de los pacientes afectados de DI de causa no explicada&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Dada la reciente incorporaci&#243;n del array-CGH a la pr&#225;ctica cl&#237;nica&#44; todav&#237;a hay muchas limitaciones a la hora de llevar a cabo una correcta interpretaci&#243;n de los resultados&#44; as&#237; como la consiguiente informaci&#243;n que se les da a las familias&#46; En estudios previos reportados se detect&#243; una gran variabilidad en la misma&#44; as&#237; como en el manejo posterior de los pacientes entre diferentes profesionales<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">23</span></a>&#46; Ambos factores pueden mejorarse si cl&#237;nicos y genetistas trabajan en estrecha colaboraci&#243;n y se dise&#241;an protocolos que disminuyan la variabilidad cl&#237;nica y aumenten la calidad de la asistencia&#46; Por otra parte&#44; si a medida que la t&#233;cnica se extiende en la pr&#225;ctica diaria&#44; los resultados obtenidos se comparten y pueden ser consultados a trav&#233;s de bases de datos p&#250;blicas en conjunci&#243;n con las caracter&#237;sticas fenot&#237;picas de cada caso&#44; ser&#225; m&#225;s sencillo definir la patogenicidad de cada una de las alteraciones encontradas&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Con respecto al coste efectividad de la t&#233;cnica&#44; recientemente se ha publicado un estudio que concluye que la realizaci&#243;n de un cariotipo molecular es m&#225;s econ&#243;mico que la realizaci&#243;n de un cariotipo convencional y las subsiguientes pruebas &#40;FISH aplicado a tel&#243;meros&#44; etc&#46;&#41; y adem&#225;s se obtienen entre un 15 y un 20&#37; m&#225;s de resultados diagn&#243;sticos que por la v&#237;a tradicional<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Actualmente&#44; el test gen&#233;tico array-CGH constituye una prueba de primer orden en el estudio de la DI&#47;RGD&#44; ya que tiene un rendimiento superior a las pruebas gen&#233;ticas convencionales &#40;cariotipo&#44; FISH&#47;MLPA aplicado a tel&#243;meros&#44; etc&#46;&#41;&#46; Aunque existen factores que se asocian a detectar con mayor probabilidad reordenamientos cromos&#243;micos&#44; estos no tienen una fuerza de discriminaci&#243;n suficiente para preseleccionar los candidatos ideales para realizaci&#243;n de esta prueba&#46; En nuestro servicio hemos modificado nuestro protocolo de estudio de la DI&#47;RGD y la t&#233;cnica array-CGH se ofrece a toda la poblaci&#243;n de individuos con DI&#47;RGD de etiolog&#237;a no conocida&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Financiaci&#243;n</span><p id="par0160" class="elsevierStylePara elsevierViewall">No se ha recibido financiaci&#243;n&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicto de intereses</span><p id="par0165" class="elsevierStylePara elsevierViewall">Los autores declaran que no existe conflicto de intereses&#46;</p></span></span>"
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          "palabras" => array:4 [
            0 => "Retraso global del desarrollo"
            1 => "Discapacidad intelectual"
            2 => "Array de hibridaci&#243;n gen&#243;mica comparada"
            3 => "Resultado diagn&#243;stico"
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            0 => "Global developmental delay"
            1 => "Intellectual disability"
            2 => "Array comparative genomic hybridisation"
            3 => "Aetiological diagnosis"
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    "resumen" => array:2 [
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El retraso global del desarrollo &#40;RGD&#41; y la discapacidad intelectual &#40;DI&#41; son un motivo de consulta frecuente en la consulta de Neuropediatr&#237;a&#46; Actualmente&#44; la hibridaci&#243;n gen&#243;mica comparada constituye una de las principales t&#233;cnicas aplicadas al diagn&#243;stico de esta patolog&#237;a&#46; Resulta &#250;til determinar qu&#233; caracter&#237;sticas fenot&#237;picas se asocian a obtener un resultado etiol&#243;gico en el test gen&#233;tico&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se llev&#243; a cabo un estudio ciego pormenorizado de las caracter&#237;sticas cl&#237;nicas&#44; antropom&#233;tricas y morfol&#243;gicas de 80 individuos afectos de DI no explicada y se analiz&#243; cuales estaban asociadas a obtener un resultado etiol&#243;gico en el array-CGH&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El resultado del array fue patol&#243;gico en un 27&#44;5&#37; de los casos&#46; Los factores que se asociaron estad&#237;sticamente a tener una prueba de array-CGH patol&#243;gica fueron los antecedentes familiares de DI&#47;RGD &#40;OR&#58; 12&#44;1&#41;&#44; la presencia de malformaciones cong&#233;nitas &#40;OR&#58; 5&#44;33&#41;&#44; m&#225;s de 3 rasgos dism&#243;rficos faciales &#40;OR&#58; 20&#44;9&#41; y la hipoton&#237;a perif&#233;rica &#40;OR&#58; 3&#44;25&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Nuestros hallazgos coinciden con otras series publicadas&#46; Por lo tanto&#44; asumimos que la probabilidad de encontrar variaci&#243;n en el n&#250;mero de copias de significado patol&#243;gico mediante array-CGH aumenta si alguna de las caracter&#237;sticas anteriores est&#225; presentes en individuos afectos de DI&#47;RGD&#46;</p></span>"
        "secciones" => array:4 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Global developmental delay &#40;GDD&#41; and intellectual disability &#40;ID&#41; are frequent reasons for consultation in paediatric neurology departments&#46; Nowadays&#44; array comparative genomic hybridisation &#40;array-CGH&#41; is one of the most widely used techniques for diagnosing these disorders&#46; Our purpose was to determine the phenotypic features associated with pathological results in this genetic test&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We conducted a blind study of the epidemiological&#44; clinical&#44; anthropometric&#44; and morphological features of 80 patients with unexplained ID to determine which features were associated with pathological results in array-CGH&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Pathological results were found in 27&#46;5&#37; of the patients&#46; Factors associated with pathological results in array-CGH were a family history of GDD&#47;ID &#40;OR&#160;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#160;12&#46;1&#41;&#44; congenital malformations &#40;OR&#160;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#160;5&#46;33&#41;&#44; having more than 3 facial dysmorphic features &#40;OR&#160;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#160;20&#46;9&#41;&#44; and hypotonia &#40;OR&#160;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#160;3&#46;25&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Our findings are consistent with those reported by other published series&#46; We therefore conclude that the probability of having pathological results in array-CGH increases with the presence of any of the features mentioned above in patients with ID&#47;GDD&#46;</p></span>"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Tama&#241;o muestral final&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Del&#58; deleci&#243;n&#59; DI&#58; discapacidad intelectual&#59; Dup&#58; duplicaci&#243;n&#59; ISCN&#58; International System for Human Cytogenetics&#59; &#40;S&#41;&#58; sana&#59; Trans&#58; translocaci&#243;n&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Caso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cromosoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nomenclatura ISCN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Del&#47;dup&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tama&#241;o &#40;Mb&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&#46;&#176; genes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Herencia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">S&#237;ndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7<br>15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7p22&#46;3p22&#46;1 &#40;178&#44;208-5&#44;337&#44;472&#41; &#215; 1<br>15q26&#46;3 &#40;98&#44;010&#44;522-100&#44;201&#44;137&#41; &#215; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del &#43;<br>Dup &#40;Trans&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#44;1<br>2&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49<br>19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Madre &#40;S&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sobrecrecimiento 15q&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7<br>15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7p22&#46;3p22&#46;1 &#40;178&#44;208-5&#44;337&#44;472&#41; &#215; 3<br>15q26&#46;3 &#40;98&#44;010&#44;522-100&#44;201&#44;137&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dup &#43;<br>Del &#40;Trans&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#44;1<br>2&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52<br>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Madre &#40;S&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5q12&#46;1q13&#46;2 &#40;60&#44;681&#44;523-72&#44;278&#44;911&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2<br>X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2q31&#46;2q32&#46;3 &#40;179&#44;356&#44;437-195&#44;896&#44;363&#41; &#215; 1<br>Xq24 &#40;117&#44;798&#44;016-118&#44;563&#44;716&#41; &#215; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del<br>Dup&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#44;5<br>0&#44;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55<br>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17q12 &#40;31&#46;474&#46;318-33&#46;679&#46;670&#41; &#215; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dup&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Padre &#40;DI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Duplicaci&#243;n 17q12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7q33q36&#46;1 &#40;136&#44;934&#44;609-150&#44;618&#44;500&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">110&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15q21&#46;1q21&#46;2 &#40;45&#44;655&#44;328-48&#44;351&#44;718&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Marfan-like&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12q21&#46;1q21&#46;31 &#40;72&#44;406&#44;097-81&#44;585&#44;992&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#44;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1q21&#46;1 &#40;144&#44;475&#44;612-146&#44;290&#44;831&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Microdeleci&#243;n distal 1q21&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3q26&#46;31&#46;q26&#46;32 &#40;173&#44;671&#44;248-178&#44;466&#44;125&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#44;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15q11&#46;2q13&#46;1 &#40;23&#44;191&#44;003-28&#44;535&#44;051&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#44;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Angelman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16p11&#46;2 &#40;29&#44;581&#44;485-30&#44;098&#44;040&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Microdeleci&#243;n 16p11&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9q34&#46;11 &#40;130&#44;412&#44;070-131&#44;456&#44;837&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14q23&#46;1q23&#46;2 &#40;56&#44;543&#44;064-63&#44;459&#44;672&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#44;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1q21&#46;1 &#40;144&#44;940&#44;640-146&#44;290&#44;972&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">X-fr&#225;gil&#47;microdeleci&#243;n 1q21&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17p11&#46;2 &#40;16&#44;947&#44;482-20&#44;160&#44;197&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Smith-Magenis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15q13&#46;2q13&#46;3 &#40;28&#44;296&#44;647-30&#44;423&#44;222&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Deleci&#243;n 15q13&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8p22p21&#46;1 &#40;17&#44;232&#44;223-28&#44;832&#44;413&#41; &#215; 1<br>8p12 &#40;30&#44;382&#44;687-30&#44;501&#44;049&#41; &#215; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del<br>Dup&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#44;6<br>0&#44;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54<br>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span><br><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22q11&#46;21 &#40;19&#44;063&#44;227-19&#44;835&#44;558&#41; &#215; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dup&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Madre &#40;S&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Duplicaci&#243;n 22q11&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Xp22&#46;2 &#40;13&#44;405&#44;350-14&#44;204&#44;866&#41; &#215; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dup&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Madre &#40;S&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12q21&#46;2 &#40;74&#44;580&#44;278-75&#44;186&#44;064&#41; &#215; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">De novo</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15q11&#46;2 &#40;20&#44;317&#44;022-20&#44;768&#44;926&#41; &#215; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dup&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Madre &#40;S&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Array-CGH normal<br>&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Array-CGH<br>patol&#243;gico<br>&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Sexo &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Femenino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">68&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;538<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Edad &#40;media a&#241;os</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#44;63 &#177; 4&#44;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#44;18 &#177; 3&#44;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;595<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">HFDI &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;043<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Abortos o mortinatos &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;301<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Fecundaci&#243;n in vitro &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;645<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Embarazo gemelar &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;548<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Edad gestacional &#40;media sem &#177; DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#44;8 &#177; 2&#44;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&#44;5 &#177; 2&#44;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;006<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Prematuridad &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;202<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Test de Apgar 1 &#40;media &#177; DE&#41;&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#44;33 &#177; 1&#44;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#44;01 &#177; 2&#44;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;806<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Test de Apgar 5 &#40;media &#177; DE&#41;&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#44;58 &#177; 0&#44;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#44;33 &#177; 1&#44;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;974<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Antropometr&#237;a DE RN &#40;media &#177; DE&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Peso&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;0&#44;32 &#177; 0&#44;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;552<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Longitud&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;0&#44;23 &#177; 1&#44;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;0&#44;31 &#177; 1&#44;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;823<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Per&#237;metro cef&#225;lico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;0&#44;16 &#177; 0&#44;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;705<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Peque&#241;o para edad gestacional &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;654<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;645<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Microcefalia RN &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;496<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Antropometr&#237;a DE A &#40;media</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Peso&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;832<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Talla&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Per&#237;metro cef&#225;lico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;538<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Microcefalia grave &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;208<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ralo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Denso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Implantaci&#243;n baja&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;090<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rizado no familiar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Alteraciones en las orejas &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">57&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;187<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sin alteraciones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Grandes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Implantaci&#243;n baja&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;115<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Despegadas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Microtia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Fositas&#47;ap&#233;ndices preauriculares &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;670<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ap&#233;ndice&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fosita&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Alteraciones en la frente &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;114<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sin alteraciones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">72&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Prominente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Amplia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Alteraciones oculares &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;547<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sin alteraciones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hipertelorismo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Epicantus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Telecantus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exoftalmus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Estrabismo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Otros&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Pesta&#241;as largas y pobladas &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;341<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Alteraciones en la nariz &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;065<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sin alteraciones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Puente nasal ancho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Narinas antevertidas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Alteraciones en los labios &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60; 0&#44;001<a class="elsevierStyleCrossRefs" href="#tblfn0040"><span class="elsevierStyleSup">a&#44;b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sin alteraciones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Labio leporino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Labio superior fino&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#44;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60; 0&#44;001<a class="elsevierStyleCrossRefs" href="#tblfn0040"><span class="elsevierStyleSup">a&#44;b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Largo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">57&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Corto&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;026<a class="elsevierStyleCrossRefs" href="#tblfn0040"><span class="elsevierStyleSup">a&#44;b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Micrognatia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Retromicrognatia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Prognatismo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Alteraciones del paladar &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;123<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ojival&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Del&#58; deleci&#243;n&#59; Dup&#58; duplicaci&#243;n&#59; HFDI&#58; historia familiar de discapacidad intelectual&#59; Trans&#58; translocaci&#243;n&#59; SNC&#58; sistema nervioso central&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">Caso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Alteraci&#243;n gen&#233;tica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">HFDI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Fenotipo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Malformaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 7p22&#46;3p22&#46;1<br>Dup&#58; 15q26&#46;3 &#40;Trans&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Bajo peso&#44; micro y dolicocefalia&#46; Frente prominente&#44; hipertelorismo&#44; filtrum largo&#44; retrognatia&#46; Hexadactilia en ambos pies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Cardiaca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Dup&#58; 7p22&#46;3p22&#46;1<br>Del&#58; 15q26&#46;3<br>&#40;Trans&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Occipucio plano&#44; pelo ralo&#44; orejas de implantaci&#243;n baja&#44; labios finos&#44; filtrum largo&#44; micrognatia&#46; Hiperlaxitud articular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Pie zambo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 5q12&#46;1q13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Microcefalia&#44; frente amplia&#44; sinefridia&#44; implantaci&#243;n baja pelo&#44; pesta&#241;as largas&#44; retrognatia&#44; filtrum largo&#46; Macroglosia&#46; T&#243;rax <span class="elsevierStyleItalic">excavatum</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 2q31&#46;2q32&#46;3<br>Dup&#58; Xq24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Macrocefalia&#46; Frente amplia&#44; hipertelorismo&#44; epicantus&#44; orejas de implantaci&#243;n baja&#44; retrognatia&#44; filtrum largo&#44; labio superior fino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Cardiaca&#47;SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Dup&#58; 17q12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Hipertelorismo&#44; pesta&#241;as largas&#44; labio superior fino&#44; filtrum largo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 7q33q36&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Epicantus interno y puente nasal ancho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Fisura palatina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 15q21&#46;1q21&#46;2<br>Marfan like&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">H&#225;bito longil&#237;neo&#46; Epicantus interno&#44; pabellones auriculares despegados&#44; labio superior fino&#46; Escoliosis&#46; Hiperlaxitud articular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Urogenital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 2q21&#46;1q21&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Micro y dolicocefalia&#46; Orejas de implantaci&#243;n baja&#44; frente amplia&#44; hipertelorismo&#44; pesta&#241;as largas&#44; labio fino&#44; filtrum largo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Urogenital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 1q21&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58;3q26&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Pabellones auriculares despegados&#44; epicantus&#44; puente nasal ancho&#44; filtrum largo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 15q11&#46;2q13&#46;1<br>S&#46; Angelman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Fallo medro&#44; microcefalia&#46; Pelo rubio ralo&#46; Piel y ojos muy claros&#46; Frente amplia&#44; micrognatia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 16p11&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Talla alta&#46; Frente amplia&#44; hipertelorismo&#44; pesta&#241;as largas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Microtia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 9q34&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Orejas de implantaci&#243;n baja&#44; hipertelorismo&#44; filtrum largo&#44; micrognatia&#44; clinodactilia en ambas manos&#46; Hipertricosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 14q23&#46;1q23&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Micro y plagiocefalia&#44; orejas de implantaci&#243;n baja&#44; frente amplia&#44; epicantus&#44; labios finos&#44; filtrum corto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 1q21&#46;1<br>S&#46; X fr&#225;gil&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Microcefalia&#44; frente amplia&#44; pabellones auriculares despegados&#44; hipertelorismo&#44; filtrum largo&#44; retromicrognatia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 17p11&#46;2<br>S&#46; Smith-Magenis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Conductas agresivas&#44; trastorno del sue&#241;o&#46; Orejas de implantaci&#243;n baja&#44; hipertelorismo&#44; prognatismo&#46; Braquidactilia&#46; Malposici&#243;n dental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 15q13&#46;2q13&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 8p22p21&#46;1<br>Dup&#58; 8p12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Occipucio plano&#44; orejas de implantaci&#243;n baja&#44; hipertelorismo&#44; narinas antevertidas&#44; filtrum largo&#46; T&#243;rax en escudo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Dup&#58; 22q11&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Dup&#58; Xp22&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Fallo medro&#44; microcefalia&#44; Frente amplia&#44; labio superior fino con filtrum largo&#46; Tetraparesia esp&#225;stico dist&#243;nica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Del&#58; 12q21&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Frente amplia&#44; hipoplasia malar&#44; paladar ojival&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">Dup&#58; 15q11&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="middle">SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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Información del artículo
ISSN: 02134853
Idioma original: Español
DOI:10.1016/j.nrl.2016.03.006
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