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Isocromosomas X: diagnóstico tardío de síndrome de Turner e133

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Figura 1 Cariotipo con isocromosoma X.En todas las metafases estudiadas se observan 46 cromosomas. Se observa alteración estructural consistente en un isocromosomade los brazos largos de uno de los cromosomas X, variante de síndrome de Turner.

Es conocido que el síndrome de Turner ocasiona talla bajapor pérdida de genes críticos relacionados con la talla pre-sentes en el cromosoma X. La talla baja presente en el 100%de los casos es punto de partida del diagnóstico al ser enocasiones el único síntoma. Sin embargo, la talla nal sueleguardar relación con la talla media parental, por lo queaquellos pacientes que se encuentren en percentiles supe-riores al p50 de la población serán quienes tengan mayordemora diagnóstica, especialmente si no se observan otrasmanifestaciones fenotípicas.

Algunas pacientes por tanto no serán diagnosticadas

hasta

el inicio

de

la pubertad,

donde

el

potencial

de

cre-cimiento perdido será mayor, ya que aun no habrán recibidotratamiento con GH, privándoseles de la ganancia de tallanal que conlleva.

Los factores que más inuyen en los resultados de tra-tamiento con GH son la edad de inicio, la duración deltratamiento y la dosis recibida antes de la estrogenización,por lo que el diagnóstico precoz es un objetivo primordialdel médico clínico.

El inicio de la terapia con hormona de crecimiento debeestar indicado en el momento en el que la talla de lapaciente con síndrome de Turner se encuentra por debajodel percentil 5 con relación a su edad, lo que acontecehabitualmente entre los 2-5 años2. Además, el inicio del

tratamiento mejora la composición corporal, aumentandola masa magra y disminuyendo la masa grasa 3.

De hecho, se ha demostrado que el inicio precoz de laterapia con hormona de crecimiento en niñas con síndromede Turner mejora e incluso normaliza la talla nal en algunoscasos 4---7 . De igual forma, el inicio tardío de este tratamientoen pacientes con edades comprendidas entre los 10-13 añosconlleva un aumento de talla de entre 2,1 y 7 cm respectoa los controles no tratados 8,9 , por lo que el benecio siguesiendo favorable aunque en menor cuantía.

Más de un tercio de los pacientes con síndrome deTurner tienen algún grado de mosaicismo 10---12 . La iden-ticación genotípica del mismo depende directamente

del método utilizado para su diagnóstico, variando desdeun 34% con técnicas citogenéticas convencionales hasta un60% con técnicas de hibridación in situ con uorescencia 13.Clásicamente se asocia la presencia de isocromosomas Xcon ausencia de anomalías congénitas, y con alta tasa deenfermedades autoinmunes (enfermedad de Crohn, tiroidi-tis linfocitaria) y sordera, lo que podría conllevar un retrasodiagnóstico como en los casos presentados 14,15 . Las con-secuencias fenotípicas de estos isocromosomas dependende 2 factores: la naturaleza de los genes que se han per-dido y el porcentaje de células 45, X; Asimismo, tampoco

se

encuentran

prácticamente

nunca

formando

mosaicismoscon poblaciones XY normales, lo que traduce el hecho deque la anormalidad cromosómica tiene origen en la meiosispaternal 16,17 .

En cualquier caso, la talla baja del síndrome de Turnerradica en la haploinsuciencia del gen SHOX en el brazocorto del cromosoma X, por lo que cuando existen isocro-mosomas de los brazos largos del cromosoma X la talla bajaes un hallazgo común a todos ellos 18---20 . Otros hallazgosfenotípicos relacionados con haploinsuciencia genética enpacientes con isocromosoma Xq son la alteración de geneslinfogénicos, y su manifestación craneofacial y cervical porcompresión del sistema linfático. Otras manifestaciones enrelación con esta alteración linfogénica serían la presen-

cia de metacarpianos cortos, cúbito valgo o micrognatia,aunque se dan en menor proporción que en pacientes conmonosomía X19,20 .

Nuestras 2 pacientes muestran una talla genética de163,2 ± 5 cm y 171,5 ± 5 cm, que se encuentran en per-centiles medios-elevados de la población; por lo queel potencial de crecimiento perdido puede no ser tanobvio como en aquellos casos en los que la talla mediapaternal esté en percentiles inferiores. Además, ambaspresentan escasa manifestación fenotípica del síndromede Turner, por lo que todo ello pudo conducir a unretraso en la sospecha diagnóstica hasta edades más tar-días.

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e134 M. Cuesta Hernández et al

Conicto de intereses

Los autores declaran no tener ningún conicto de intereses.

Bibliografía

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15. Azcona C, Bareille P, Stanophe R. Lesson of the week: Tur-ner ś syndrome mosaicism in patients with a normal blood lym-phocyte karyotype. Br Med J. 1999;318:856 ---7.

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