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Sin embargo&#44; existen hasta 10 formas al&#233;licas de los genes FGFR que manifiestan craneosinostosis y&#44; aunque cada entidad tiene un fenotipo bastante particular&#44; algunos de los signos cl&#237;nicos son superponibles y con expresividad variable<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> pudiendo resultar dif&#237;cil la clasificaci&#243;n de algunos pacientes&#46; Para simplificarlo&#44; en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se esquematizan los signos cl&#237;nicos m&#225;s caracter&#237;sticos de cada entidad&#44; haci&#233;ndose tambi&#233;n referencia a los genes responsables de cada una y al porcentaje actual de detecci&#243;n de las mutaciones<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p id="par0015" class="elsevierStylePara elsevierViewall">En el Servicio de Pediatr&#237;a del Consorci Sanitari de Terrassa&#44; desde 1990 hasta la actualidad hemos diagnosticado un total de 12 pacientes con craneosinostosis&#58; 8 formas aisladas y 4 sindr&#243;micas &#40;un s&#237;ndrome de Apert&#44; un s&#237;ndrome de Baller-Gerold y 2 s&#237;ndromes de Crouzon&#41;&#46; Estos 2 &#250;ltimos&#44; diagnosticados en 2008 y 2009&#44; fueron derivados para tratamiento quir&#250;rgico al Servicio de Neurocirug&#237;a del Hospital Sant Joan de D&#233;u &#40;Esplugues de Llobregat&#41; y son el objeto de esta revisi&#243;n&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Resultados</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Paciente 1</span><p id="par0020" class="elsevierStylePara elsevierViewall">Ni&#241;a de 35 d&#237;as de vida&#44; remitida por presentar abombamiento de la fontanela durante las &#250;ltimas semanas con aumento del per&#237;metro craneal&#44; pasando de &#43;2 DE de reci&#233;n nacida hasta &#43;3 DE&#46; Antecedentes familiares&#58; primer hijo&#59; padres con morfolog&#237;a y per&#237;metro craneal normales&#59; un aborto espont&#225;neo anterior&#46; Antecedentes personales&#58; embarazo con diabetes gestacional y parto a las 40 semanas mediante ces&#225;rea&#46; Test de Apgar 9-10&#46; Peso&#58; 3&#46;410 g &#40;pc 40&#41;&#44; longitud&#58; 49&#44;5<span class="elsevierStyleHsp" style=""></span>cm &#40;pc 40&#41;&#44; per&#237;metro cef&#225;lico&#58; 36&#44;5<span class="elsevierStyleHsp" style=""></span>cm &#40;pc 98&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">En la exploraci&#243;n destacaba un per&#237;metro cef&#225;lico de 39&#44;3<span class="elsevierStyleHsp" style=""></span>cm &#40;&#43;3 DE&#41;&#44; con frente prominente&#44; moderada dolicocefalia&#44; marcado hipertelorismo ocular con proptosis y estrabismo divergente&#46; Manos y pies&#44; normales&#46; Fontanela ligeramente abombada&#44; palp&#225;ndose un ribete en la sutura sagital&#46; Su fenotipo facial concordaba con un s&#237;ndrome de Crouzon&#46; Rx craneal con sinostosis sagital &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Fondo de ojo normal&#46; Precis&#243; intervenci&#243;n quir&#250;rgica a los 3 y 8 meses por agravamiento evolutivo de su morfolog&#237;a cr&#225;neo-facial y desarrollo de pansinostosis&#46; La segunda intervenci&#243;n consisti&#243; en un avance fronto-orbitario&#46; Tras 21 meses de seguimiento&#44; mantiene normalidad en su desarrollo psicomotor con mejor&#237;a evidente de su fenotipo craneo-facial&#46; Mediante secuenciaci&#243;n de los exones 8 y 10 del gen FGFR2 y del ex&#243;n 6 del gen FGFR3 no se encontraron mutaciones&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Paciente 2</span><p id="par0030" class="elsevierStylePara elsevierViewall">Ni&#241;o de 3 a&#241;os y 8 meses de edad&#44; remitido para estudio de cefaleas intermitentes de tipo migra&#241;oso&#44; de un a&#241;o de evoluci&#243;n&#46; Antecedentes familiares&#58; padres y hermana con morfolog&#237;a y per&#237;metro craneal normales&#46; Antecedentes personales&#58; embarazo y parto normales&#46; Peso&#58; 3&#46;100 g &#40;pc 25&#41;&#44; longitud&#58; 49<span class="elsevierStyleHsp" style=""></span>cm &#40;pc 25&#41;&#44; per&#237;metro cef&#225;lico&#58; 35&#44;5<span class="elsevierStyleHsp" style=""></span>cm &#40;pc 60&#41;&#46; Bronquitis obstructivas de lactante&#46; Obesidad desde los 12 meses&#46; Deambul&#243; a los 2 a&#241;os&#46; Leves dificultades de pronunciaci&#243;n&#46; Intelecto normal&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">En la exploraci&#243;n destacaba obesidad&#44; con un peso de 29<span class="elsevierStyleHsp" style=""></span>kg &#40;&#43;7 DE&#41;&#44; talla de 104&#44;5<span class="elsevierStyleHsp" style=""></span>cm &#40;&#43;1&#44;5 DE&#41; y per&#237;metro craneal de 50&#44;6<span class="elsevierStyleHsp" style=""></span>cm &#40;0 DE&#41;&#46; Presentaba una leve proptosis ocular y en el fondo de ojo exist&#237;a un discreto borramiento de los bordes papilares&#46; En la Unidad de Endocrinolog&#237;a se detect&#243; acantosis <span class="elsevierStyleItalic">nigricans</span> en el cuello y las axilas&#44; manifestada a partir de los 2 a&#241;os &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46; Rx de cr&#225;neo y TC cerebral con evidentes impresiones digitales &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; El fenotipo cr&#225;neo-facial y la anomal&#237;a dermatol&#243;gica hicieron sospechar un s&#237;ndrome de Crouzon con acantosis <span class="elsevierStyleItalic">nigricans</span>&#46; Los potenciales evocados visuales y la RM cerebral fueron normales&#46; Transcurridos 18 meses&#44; apareci&#243; edema de papila en el fondo de ojo y la TC craneal detect&#243; pansinostosis&#44; incluida levemente la met&#243;pica&#46; Se intervino quir&#250;rgicamente realiz&#225;ndose un avance fronto-supraorbitario&#44; respetando las &#243;rbitas dado que no eran muy peque&#241;as&#44; junto a una fragmentaci&#243;n biparietal&#44; consigui&#233;ndose aumentar el volumen intracraneal&#46; Tras 2 a&#241;os se mantiene asintom&#225;tico y se ha reducido la proptosis ocular&#46; No ha sido posible el estudio gen&#233;tico por haberse trasladado a otra comunidad aut&#243;noma&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discusi&#243;n</span><p id="par0040" class="elsevierStylePara elsevierViewall">Estos 2 pacientes presentan 2 formas diferentes de s&#237;ndrome de Crouzon&#44; el primero atribuido a una mutaci&#243;n en el gen FGFR2 &#40;detect&#225;ndose la misma al menos en la mitad de los pacientes<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44; sin hallarla en nuestro caso&#41; y el segundo en FGFR3 &#40;una mutaci&#243;n recurrente&#44; aunque no la hemos podido estudiar en el nuestro&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Si el estudio del gen FGFR2 en un paciente con sospecha de s&#237;ndrome de Crouzon se realiza antes de los 2-3 a&#241;os&#44; las probabilidades de obtener un resultado negativo ser&#225;n mayores que si se realiza a una edad posterior&#44; por la posibilidad de se trate de un s&#237;ndrome de Crouzon con acantosis <span class="elsevierStyleItalic">nigricans</span> sin que todav&#237;a se haya manifestado la anomal&#237;a cut&#225;nea&#44; localiz&#225;ndose la mutaci&#243;n en FGFR3&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Crouzon describi&#243; en 1992 a una madre y su hija afectadas por una craneosinostosis que abarcaba diversas suturas&#44; provocando una deformidad cr&#225;neo-facial junto a exoftalmos&#46; Posteriores publicaciones m&#233;dicas de casos similares configurar&#237;an este s&#237;ndrome&#44; recibiendo el nombre del primer autor&#46; Su herencia es AD &#40;autos&#243;mica dominante&#41;&#44; con penetrancia completa y expresividad variable&#46; La mitad de los casos son debidos a mutacions <span class="elsevierStyleItalic">de novo&#46;</span> Se estima una incidencia de 1 por cada 60&#46;000 reci&#233;n nacidos vivos y constituye el 4&#44;8&#37; de todas las craneosinostosis&#46; No tiene predominio racial ni de sexo&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">La craneosinostosis suele detectarse durante el primer a&#241;o de vida y puede abarcar la b&#243;veda craneal&#44; base de cr&#225;neo&#44; &#243;rbitas y complejo maxilar&#46; La precocidad y el orden de afectaci&#243;n de las suturas pueden variar&#44; existiendo una cierta diversidad en su espectro cl&#237;nico&#46; Destaca principalmente hipertelorismo con exoftalmos &#40;por &#243;rbitas poco profundas&#41;&#44; estrabismo divergente&#44; nariz en pico curvado&#44; labio superior fino&#44; hipoplasia mediofacial &#40;por maxilar superior reducido&#41; y un relativo prognatismo&#46; En raras ocasiones tambi&#233;n pueden existir anomal&#237;as oculares&#46; Un 7&#37; de los casos son muy graves<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44; adquiriendo el cr&#225;neo una forma trilobulada &#40;tambi&#233;n llamada trigonocefalia&#44; en &#171;hoja de tr&#233;bol&#187;&#44; &#171;clover-leaf&#187; o &#171;kleeblattsch&#228;del&#187;&#41;&#46; Si se demora la cirug&#237;a de estos casos&#44; la hipertensi&#243;n intracraneal y el edema de papila provocan grave d&#233;ficit visual&#46; Un 47&#37; tambi&#233;n presenta hidrocefalia progresiva&#44; con posible herniaci&#243;n amigdalar y&#47;o siringomielia&#46; Algunos centros tratan la hidrocefalia mediante ventriculostom&#237;a endosc&#243;pica en el tercer ventr&#237;culo&#44; evitando la colocaci&#243;n de una v&#225;lvula derivativa en m&#225;s de la mitad de los casos<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; El 12&#37; de los casos presentan retraso cognitivo&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Existe un espectro cl&#237;nico muy amplio para este s&#237;ndrome&#44; cuya forma de presentaci&#243;n m&#225;s grave es neonatal&#46; En ocasiones&#44; el estudio cl&#237;nico familiar puede desvelar casos muy leves en el adulto&#44; que no requieren ning&#250;n tratamiento&#46; En los casos severos la cirug&#237;a debe ser precoz&#44; anticip&#225;ndose a posibles complicaciones&#44; especialmente las del nervio &#243;ptico<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; Una de las t&#233;cnicas consiste en realizar un avance fronto-orbitario&#44; que evitar&#225; la hipertensi&#243;n intracraneal&#44; aparte de mejorar la est&#233;tica&#46; Mediante la t&#233;cnica quir&#250;rgica Le Fort III se ha demostrado evidente mejor&#237;a de los par&#225;metros respiratorios para tratar las apneas obstructivas durante el sue&#241;o<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; En una segunda fase se puede tratar la hipoplasia maxilar mediante un avance cigom&#225;tico-maxilar&#46; Se consideran de inter&#233;s los estudios campim&#233;tricos&#44; capaces de evidenciar d&#233;ficits que los estudios de visi&#243;n central no detectan<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46; Requieren un seguimiento interdisciplinar&#44; abarcando tambi&#233;n factores psicol&#243;gicos para facilitar su integraci&#243;n social<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Es necesario el asesoramiento gen&#233;tico dado que el riesgo de recurrencia para el afectado es del 50&#37; en cada gestaci&#243;n&#44; sin poder predecir su gravedad&#46; El estudio gen&#233;tico prenatal y&#47;o preimplantacional solo puede realizarse cuando se conoce la mutaci&#243;n patog&#233;nica del caso &#237;ndice&#46; La ecograf&#237;a prenatal de alta resoluci&#243;n puede detectar el exoftalmos o el hipertelorismo&#59; sin embargo&#44; la craneosinostosis solo es detectable mediante ecograf&#237;a tridimensional o resonancia magn&#233;tica &#40;RM&#41;&#46; En las formas <span class="elsevierStyleItalic">de novo</span>&#44; al no poder descartarse un mosaicismo germinal&#44; el riesgo de recurrencia para los padres en futuros embarazos se estima inferior al 3&#37;&#44; por lo que se aconseja realizar estudio prenatal<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Del resto de entidades al&#233;licas de los genes FGFR1&#44; FGFR2 y FGFR3 que tienen en com&#250;n la craneosinostosis&#44; se resume a continuaci&#243;n lo m&#225;s caracter&#237;stico de cada s&#237;ndrome&#44; orden&#225;ndose&#44; como en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#44; en primer lugar los afectados por FGFR2 y otros posibles genes&#44; y al final los afectados por FGFR3&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">El s&#237;ndrome de Apert &#40;MIM 101200&#41; es debido a mutaciones heterocigotas del <span class="elsevierStyleItalic">gen FGFR2</span>&#44; de herencia AD&#44; aunque predominan los casos debidos a mutaci&#243;n <span class="elsevierStyleItalic">de novo&#46;</span> Lo m&#225;s caracter&#237;stico es la presencia de sindactilia severa en las manos y los pies&#46; Son frecuentes las malposiciones dentales con dientes api&#241;ados<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">El s&#237;ndrome de Pfeiffer &#40;MIM 101600&#41; es debido a mutaciones del gen <span class="elsevierStyleItalic">FGFR2</span> &#40;Pfeiffer tipo 2&#41; &#40;MIM 176943&#41; y m&#225;s raramente del <span class="elsevierStyleItalic">FGFR1</span> &#40;8p12-p11&#46;2&#41; &#40;Pfeiffer tipo 1&#41; &#40;MIM 136350&#41;&#46; Descrito en 1964&#44; se han publicado poco m&#225;s de 60 casos&#46; De herencia AD&#44; con penetrancia y expresividad variable incluso intrafamiliar &#40;se han descrito familias en las que un miembro padec&#237;a afectaci&#243;n digital sin craneosinostosis&#44; y en otro miembro al rev&#233;s o con m&#237;nima afectaci&#243;n&#41;&#46; Se conoce la existencia de que una misma mutaci&#243;n en <span class="elsevierStyleItalic">FGFR2</span> con fenotipo Pfeiffer&#44; se haya descrito previamente con fenotipo Crouzon&#44; Jackson-Weiss o Saethre-Chotzen<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">El s&#237;ndrome de Jackson-Weiss &#40;MIM 123150&#41; se debe a mutaciones del gen <span class="elsevierStyleItalic">FGFR2</span>&#46; Solo un paciente descrito con una mutaci&#243;n &#40;P252R&#41; en el gen <span class="elsevierStyleItalic">FGFR1</span> &#40;8p11&#46;2-p11&#46;1&#41;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46; De herencia AD&#44; tambi&#233;n con gran variabilidad de la expresividad intrafamiliar&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">El s&#237;ndrome de Saethre-Chotzen &#40;tambi&#233;n llamado cr&#225;neo-&#243;culo-dental&#41; &#40;MIM 101400&#41; se debe a mutaciones del gen TWIST1 &#40;m&#225;s de 35 conocidas y detectables en un 75&#37;&#41;&#44; y a mutaciones del gen <span class="elsevierStyleItalic">FGFR2</span>&#44; habi&#233;ndose descrito solo 2 familias<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a>&#46; Aunque se ha estimado una incidencia entre 1&#58;25&#46;000 y 1&#58;50&#46;000 reci&#233;n nacidos vivos&#44; su frecuencia real se cree mayor por la existencia de pacientes sin diagnosticar con solo signos menores&#46; Por otro lado&#44; los avances gen&#233;ticos han permitido constatar que en algunas casu&#237;sticas se inclu&#237;a err&#243;neamente a pacientes que padec&#237;an en realidad s&#237;ndrome de Muenke&#44; cuyo fenotipo puede ser similar<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; La craneosinostosis suele requerir tratamiento quir&#250;rgico precoz y casi la mitad de los pacientes precisan nuevas intervenciones antes de los 5 a&#241;os al reaparecer la hipertensi&#243;n intracraneal<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">El s&#237;ndrome de Antley-Bixler se debe a mutaciones en el gen <span class="elsevierStyleItalic">FGFR2</span>&#44; de herencia AD&#46; Recientemente&#44; se ha descrito genitales ambiguos en ambos sexos por deficiencia del citocromo P450 oxidoreductasa &#40;POR&#41;&#44; responsable de la s&#237;ntesis de esteroides<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; En estos nuevos casos se han podido encontrar mutaciones en el gen <span class="elsevierStyleItalic">POR</span> &#40;7q11&#46;2&#41;&#44; de herencia AR &#40;autos&#243;mica recesiva&#41;&#46; Se han descrito mutaciones de este gen manifestando solo insuficiencia adrenal o infertilidad&#44; sin dismorfias&#44; y menor capacidad para metabolizar los f&#225;rmacos que utilizan dicha v&#237;a metab&#243;lica<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">El s&#237;ndrome de Beare-Stevenson es debido a un defecto del <span class="elsevierStyleItalic">gen FGFR2</span> &#40;se conocen 3 mutaciones <span class="elsevierStyleItalic">de novo</span>&#41;&#44; o tambi&#233;n del <span class="elsevierStyleItalic">FGFR3</span>&#46; Solo se han descrito 12 casos espor&#225;dicos desde la primera descripci&#243;n en 1969&#46; Son caracter&#237;sticas las anomal&#237;as cut&#225;neas como <span class="elsevierStyleItalic">cutis gyrata</span> &#40;arrugas y piel sobrante&#41; en cr&#225;neo&#44; cara y extremidades&#44; y acantosis <span class="elsevierStyleItalic">nigricans</span>&#46; El primer paciente descrito por Beare en 1969 y otros 2 casos<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> presentaban dientes neonatales con posterior hipodontia&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">El s&#237;ndrome de Crouzon con acantosis <span class="elsevierStyleItalic">nigricans</span> es debido a la mutaci&#243;n recurrente G1172A&#44; missense espec&#237;fica&#44; en el dominio transmembrana del gen <span class="elsevierStyleItalic">FGFR3</span>&#46; Publicados hasta la fecha 35 casos&#46; Tienen fenotipo Crouzon de diversa gravedad al que se le a&#241;ade una acantosis <span class="elsevierStyleItalic">nigricans</span> aparecida durante los primeros 2-3 a&#241;os de vida &#40;como en nuestro segundo paciente&#41;&#44; aunque se conoce un caso de presentaci&#243;n neonatal<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; El 5&#37; de los pacientes con s&#237;ndrome de Crouzon presentan acantosis <span class="elsevierStyleItalic">nigricans</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; Se puede localizar en la regi&#243;n posterior del cuello&#44; espalda&#44; axilas&#44; ingles&#44; perioral&#44; periorbitaria&#44; pliegues nasolabiales&#44; t&#243;rax o abdomen&#46; Puede evolucionar en a&#241;os a una hiperplasia verrucosa&#46; Se ha descartado una insensibilidad a la insulina&#44; siendo la hip&#243;tesis m&#225;s probable una disfunci&#243;n de melanocitos&#44; raramente cementomas mandibulares o desmoosteoblastomas<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; Tiene un amplio espectro cl&#237;nico por probable existencia de genes modificadores<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a>&#46; Se ha descrito otra mutaci&#243;n en el mismo gen&#44; tambi&#233;n de herencia AD&#44; en la que solo se expresa la anomal&#237;a cut&#225;nea&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">El s&#237;ndrome de Muenke tambi&#233;n es debido a una mutaci&#243;n recurrente &#40;P250R&#41; del gen <span class="elsevierStyleItalic">FGFR3</span><a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#44; de herencia AD&#44; con baja penetrancia y expresividad muy variable&#46; Un 61&#37; son casos espor&#225;dicos&#46; Se han publicado m&#225;s de 300 casos&#46; Es muy frecuente la sordera&#44; especialmente para bajas frecuencias&#44; y retraso psicomotor en la mitad de los pacientes&#46; Posible dismorfismo sexual en varones&#46; Una mutaci&#243;n diferente en el mismo gen&#44; la P250L&#44; da lugar a un fenotipo muy similar a Muenke&#46; Se han descrito casos en los que el &#250;nico s&#237;ntoma cl&#237;nico es la sordera&#46; Es muy importante la confirmaci&#243;n gen&#233;tica&#44; especialmente en los casos con poca expresividad cl&#237;nica&#44; permitiendo realizar un correcto asesoramiento gen&#233;tico<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Existe a&#250;n otra entidad denominada <span class="elsevierStyleItalic">osteoglophonic dwarfism</span> &#40;o enanismo en &#171;sacabocados&#187;&#41; &#40;8p11&#46;1-p11&#46;2&#41; &#40;MIM 66250&#41;&#44; con fenotipo de acondroplasia pero asociando tambi&#233;n craneosinostosis y lesiones qu&#237;sticas metafisarias aparecidas generalmente en la etapa adulta&#46; Al resultar el nanismo el signo gu&#237;a principal&#44; no la hemos incluido en la tabla&#44; pero tambi&#233;n constituye otra craneosinostosis al&#233;lica de cualquiera de los genes FGFR1&#44; FGFR2 o FGFR3&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; las craneosinostosis pueden presentarse aisladas o formar parte de un s&#237;ndrome complejo&#46; En el primer grupo&#44; un 10-14&#37; tambi&#233;n son de causa gen&#233;tica&#46; En las formas sindr&#243;micas es necesario detallar los signos cl&#237;nicos pues en ocasiones pueden orientar el diagn&#243;stico&#46; Sin embargo&#44; dada la frecuente existencia de signos cl&#237;nicos comunes entre algunas de las entidades&#44; es recomendable realizar el estudio molecular para intentar confirmarlo&#44; lo que permitir&#225; ofrecer a las familias un correcto asesoramiento gen&#233;tico<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; A partir de los 2 pacientes presentados con fenotipo Crouzon&#44; se han esquematizado los s&#237;ndromes craneoesten&#243;ticos que son formas al&#233;licas de los genes FGFR1&#44; FGFR2 y FGFR3&#44; resumi&#233;ndose en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> los principales aspectos cl&#237;nicos&#44; genes implicados y porcentaje de detecci&#243;n de mutaciones<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44; siendo tambi&#233;n llamativa su amplia heterogeneidad gen&#233;tica y al&#233;lica&#46; Ser&#225;n necesarias m&#225;s investigaciones para profundizar en la fisiopatolog&#237;a de estas entidades e intentar mejorar la relaci&#243;n fenotipo-genotipo&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflictos de intereses</span><p id="par0125" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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            1 => "Antley-Bixler"
            2 => "Apert"
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            6 => "FGFR1"
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            11 => "Osteoglophonic dwarfism"
            12 => "Pfeiffer"
            13 => "Saethre-Chotzen"
          ]
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    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La craneosinostosis consiste en una fusi&#243;n patol&#243;gica precoz de una o varias suturas craneales&#46; El 20&#37; de los casos corresponde a formas sindr&#243;micas con patrones hereditarios mendelianos&#44; mientras que el 80&#37; restante a formas no sindr&#243;micas&#44; pero con transmisi&#243;n hereditaria en el 10-14&#37; de los casos&#46; A prop&#243;sito de 2 pacientes con s&#237;ndrome de Crouzon&#44; se revisan los aspectos cl&#237;nicos y gen&#233;ticos&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Paciente 1&#58; ni&#241;a de 35 d&#237;as con macrocefalia progresiva&#44; abombamiento de la fontanela&#44; proptosis ocular&#44; hipertelorismo y estrabismo divergente&#46; Rx de cr&#225;neo con sinostosis de la sutura sagital&#46; Fue intervenida quir&#250;rgicamente a los 3 y 8 meses por desarrollo de pansinostosis&#46; Paciente 2&#58; ni&#241;o de 3 a&#241;os 8 meses con cefaleas de tipo migra&#241;oso de un a&#241;o de evoluci&#243;n&#46; Presentaba acantosis nigricans&#46; Rx de cr&#225;neo y TC craneal con impresiones digitales y fondo de ojo con discreto borramiento papilar&#46; Tras 18 meses apareci&#243; edema de papila y en la TC craneal se detect&#243; pansinostosis&#44; requiriendo intervenci&#243;n quir&#250;rgica&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Hemos presentado un paciente con s&#237;ndrome de Crouzon cl&#225;sico &#40;paciente 1&#41; y otro con acantosis nigricans &#40;paciente 2&#41;&#44; diagnostic&#225;ndose por su particular fenotipo cl&#237;nico&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Dada la amplia diversidad de formas al&#233;licas en los genes FGFR que cursan con craneosinostosis&#44; conoci&#233;ndose hasta 10 entidades&#44; realizamos una revisi&#243;n de las mismas&#46; En las formas sindr&#243;micas&#44; como nuestros 2 casos&#44; conviene detallar al m&#225;ximo los signos cl&#237;nicos pues pueden orientar el diagn&#243;stico&#44; y el estudio molecular permitir&#225; en ocasiones confirmarlo y ofrecer asesoramiento gen&#233;tico a las familias&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Craniosynostosis is an abnormal and premature fusion of any cranial suture&#46; Twenty per cent of them involve any specific syndrome with Mendelian transmission&#59; the other 80&#37; are &#8220;non syndromic&#8221;&#44; although but 10-14&#37; of them are genetically transmitted&#46; Using the experience of two patients with Crouzon syndrome&#44; a clinical and genetic review is performed&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Patient 1&#58; girl of 35 days of age with progressive macrocephaly&#44; protrusion of fontanel&#44; ocular proptosis&#44; hypertelorism and divergent strabismus&#46; Cranial RX with sagittal synostosis&#46; Surgical operation was performed with 3 months and 8 months of age due to development of pansynostosis&#46; Patient 2&#58; boy of 3 years 8 months of age with headaches of migrainous type of one year onset&#46; He had acanthosis nigricans&#46; Cranial RX and cerebral CT with evident digital markings and fundus of eye with undefined papillary limits&#44; but 18 month later oedematous papilla were evident and pansynostosis was detected&#44; so surgery was performed&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">We present a patient with classical Crouzon syndrome &#40;patient 1&#41; and another with acanthosis nigricans &#40;patient 2&#41;&#44; both diagnosed by the description of characteristic clinical features&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Ten craniosynostotic clinical forms are currently known as allelic variations of the FGFR genes&#44; and as such have reviewed them&#46; As in our two cases&#44; in syndromic types is very important the accurate study of the phenotype to orientate the diagnosis&#44; although the molecular study will confirm it in many patients and genetic counselling offered&#46;</p>"
      ]
    ]
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        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
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        "figura" => array:1 [
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Radiograf&#237;a de perfil de cr&#225;neo del paciente 1 mostrando craneosinostosis de la sutura sagital y dolicocefalia&#46;</p>"
        ]
      ]
      1 => array:7 [
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        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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            "imagen" => "gr2.jpeg"
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Regi&#243;n posterior del cuello del paciente 2 mostrando acantosis <span class="elsevierStyleItalic">nigricans&#46;</span></p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Radiograf&#237;a de perfil de cr&#225;neo del paciente 2 mostrando impresiones digitales en los huesos del cr&#225;neo&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ac&#46; <span class="elsevierStyleItalic">nigric&#46;</span>&#58; acantosis <span class="elsevierStyleItalic">nigricans</span>&#59; ACC&#58; agenesia del cuerpo calloso&#59; acortam&#46; falang&#46;&#58; acortamiento de falanges&#59; AD&#58; autos&#243;mica dominante&#59; AR&#58; autos&#243;mica recesiva&#59; Craneos&#46; cor&#46;&#58; craneosinostosis coronal&#59; f&#233;mures curv&#46;&#58; f&#233;mures curvados&#59; fus&#46; vert&#46;&#58; fusiones vertebrales&#59; Nl&#58; normal&#59; pos&#46;&#58; posible&#59; R&#46; ment&#46;&#58; retraso mental&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">1&#46; Craneos&#46; cor&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">2&#46; S&#46; Crouzon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">3&#46; S&#46; Apert&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">4&#46; S&#46; Pfeiffer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">5&#46; S&#46; Jackson-Weiss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">6&#46; S&#46; Saethre-Chotzen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">7&#46; S&#46; Antley-Bixler&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">8&#46; S&#46; Beare-Stevenson&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">9&#46; S&#46; Crouzon con ac&#46; <span class="elsevierStyleItalic">nigric&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">10&#46; S&#46; Muenke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gen&#47;mutaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">TWIST1</span>&#44; <span class="elsevierStyleItalic">MSX2</span>&#44; <span class="elsevierStyleItalic">FGFR2</span>&#44; <span class="elsevierStyleItalic">FGFR3</span>&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">FGFR2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">FGFR2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">FGFR2</span> &#40;tipo I&#44; II&#44; III&#41; <span class="elsevierStyleItalic">FGFR1</span> &#40;5&#37; tipo I&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FGFR2 <span class="elsevierStyleItalic">FGFR1</span> &#40;un caso&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TWIST1 <span class="elsevierStyleItalic">FGFR2</span> &#40;2 famil&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">FGFR2</span> &#40;AD&#41; <span class="elsevierStyleItalic">POR</span> &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">FGFR2</span> &#40;mayor&#237;a&#41; <span class="elsevierStyleItalic">FGFR3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FGFR3 &#40;G1172A&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">FGFR3</span> &#40;P250R&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Detec&#46; mut&#46;<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; en <span class="elsevierStyleItalic">FGFR2 y FGFR 3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62; 50&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62; 98&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#37; en cada tipo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37; desconocido&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#37; en <span class="elsevierStyleItalic">TWIST1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37; desconocido&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37; desconocido&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Herencia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD &#40;<span class="elsevierStyleItalic">FGFR2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Desconocida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dismorfia craneo-facial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Craneal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ptosis palpebr&#46;&#44; hipertelorismo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cr&#225;neo forma trapezoide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sinostosis solo coronal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Trigonocefalia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Raramente &#40;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Raramente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#171;Lagunas&#187; parietales&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Manos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posibles anomal&#237;as Rx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sindactilia cut&#225;nea &#40;posible &#243;sea&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Braquidactilia&#44; sindactilia 2-3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl la mayor&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Braquidactilia&#44; sindactilia 2-3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Camptodactilia&#44; aracnodactilia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible leve acortam&#46; falang&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Braquidactilia&#44; posible fusi&#243;n en carpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pulgares&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cortos &#40;ocasional sindactilia&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anchos&#44; cortos &#40;desviaci&#243;n medial&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anchos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posibles anomal&#237;as falanges&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polidactilia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible en manos y pies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Falange distal b&#237;fida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antebrazos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible sublux&#46; cabeza radio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible sinostosis radio-humeral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sinostosis radio-cubital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Curvados&#44; sinostosis radio-cubital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Codos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible anquilosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible limitac&#46; extensi&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sinostosis radio-humeral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible limitac&#46; extensi&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sinostosis radio-humeral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sindactilia cut&#225;nea &#40;posible &#243;sea&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cortos &#40;posible sinsactilia&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sinost&#46; tarsiana&#44; sindac&#46; cut&#46; 2-3&#46; 1&#46;<span class="elsevierStyleSup">er</span> metat&#46; corto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sindactilia 3-4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posibles zambos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible fusi&#243;n tarso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;<span class="elsevierStyleSup">er</span> dedo pie&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Separados &#40;ocasional sindactilia&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anchos y cortos&#44; <span class="elsevierStyleItalic">hallux varus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anchos&#44; <span class="elsevierStyleItalic">hallux varus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anchos&#44; <span class="elsevierStyleItalic">hallux valgus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible ancho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Card&#237;aco&#44; renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible afectaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible afectaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible afectaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible afectaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible afectaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hidrocef&#46; &#40;47&#37;&#41;&#44; R&#46; ment&#46; &#40;12&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posibles hidrocefalia&#44; ACC y Chiari I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible hidrocefalia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intelecto en general Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible normalidad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible Chiari e hidrocefalia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible hidrocefalia o Chiari I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R&#46; ment&#46; &#40;50&#37;&#41; &#40;pos&#46; megalen- cefalia aislada&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Piel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cutis girata&#44; acantosis <span class="elsevierStyleItalic">nigricans</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acantosis <span class="elsevierStyleItalic">nigricans</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sordera&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible esten&#46; canal auditivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&#59; displasia auricular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible displasia auricular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Si &#40;neuro-sens&#46; o mixta&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Otros&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chiari I &#40;73&#37;&#41;&#44; fus&#46; vert&#46; &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fus&#46; vert&#46; &#40;68&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Muy amplio espectro cl&#237;nico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&#233;mures curv&#46; Posib&#46; genitales ambiguos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posible anomal&#46; genital&#44; dental y hernia umbilic&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pos&#46; atr&#46; coanas&#44; fisura palatina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Muy amplio espectro cl&#237;nico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Formas al&#233;licas de los genes <span class="elsevierStyleItalic">FGFR1</span>&#44; <span class="elsevierStyleItalic">FGFR2</span> y <span class="elsevierStyleItalic">FGFR3</span> que cursan con craneosinostosis</p>"
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                          "etal" => true
                          "autores" => array:6 [
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                    0 => array:1 [
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                        "tituloSerie" => "Am J Med Genet"
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            13 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetic heterogeneity of Saethre-Chotzen syndrome&#44; due to TWIST and FGFR mutations"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;A&#46; Paznekas"
                            1 => "M&#46;L&#46; Cunningham"
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                            4 => "M&#46;H&#46; Lipson"
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