La evolución tecnológica en genómica tiene una velocidad muy rápida y las guías clínicas se quedan obsoletas respecto a la práctica clínica habitual, de forma que los profesionales frecuentemente nos encontramos con preguntas difíciles de responder.

Mucho ha llovido desde las guías de la AAN de 2003, en las que se propuso como primer escalón para el estudio del retraso global del desarrollo y los trastornos del espectro del autismo la utilización del cariotipo y el X-fragil, actualmente retiradas , tras la revisión realizada en 2011 por los mismos autores .

Las guías de 2012 de la academia americana de pediatría, introdujeron por primera vez el uso sistemático del aCGH . Una consecuencia no inesperada, ha sido la progresiva decadencia de las técnicas de citogenética tradicionales (cariotipo), hasta el punto de que se está perdiendo el “know how”, y el número de profesionales capaces de realizar la técnica está en riesgo de extinción.

Desde entonces, la aparición de los estudios de secuenciación del exoma ha significado una revolución desde el punto de vista del incremento de la rentabilidad diagnóstica (diagnostic yield). En particular, la aparición de sistemas bioinformáticos de detección de CNV a partir de los datos obtenidos en la secuenciación del exoma, ha permitido cuestionar seriamente la utilidad de realizar un aCGH previo.

En las últimas guías de la ACMG de 2021, se ha analizado si el exoma debería ser el 1º escalón en el estudio diagnóstico de los pacientes con malformaciones congénitas múltiples y discapacidad intelectual, proponiendo un cambio en el paradigma actual.

No obstante, continua existiendo discusión en el campo respecto a cuál debe ser la actual secuencia de decisiones desde el punto de vista de la práctica clínica, cuestionandose tímidamente si realmente es rentable continuar realizando X-fragil a toda la población, dada la disminución de prevalencia identificada en las últimas décadas .

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