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Baja penetración en el síndrome de QT largo: impacto clínico

S G Priori¹, C Napolitano, P J Schwartz

¹Molecular Cardiology and Electrophysiology Laboratory, Fondazione "Salvatore Maugeri" IRCCS, Pavia, Italy. spriori@fsm.it

|February 2, 1999

Resumen

Muchos pacientes con síndrome de QT largo (SQTL) son portadores de genes silenciosos, lo que desafía el diagnóstico tradicional. El cribado molecular es crucial para identificar a estas personas y a sus familiares en riesgo.

Área de la Ciencia:

Cardiología Cardiología.
Genética La genética.
Diagnóstico molecular El diagnóstico molecular es el diagnóstico molecular.

Sus antecedentes:

El síndrome del intervalo QT largo (LQTS) se diagnostica típicamente por la prolongación del intervalo QT o los síntomas clínicos.
Las suposiciones anteriores sugerían una tasa de penetración del 90% para LQTS.
Este estudio investigó la hipótesis de que muchos pacientes con LQTS son portadores asintomáticos.

Objetivo del estudio:

Para determinar la prevalencia de portadores de genes asintomáticos en familias con LQTS.
Evaluar la penetración de LQTS en familias con casos aparentemente esporádicos.
Para evaluar la efectividad de los criterios de diagnóstico clínico frente al diagnóstico molecular.

Principales métodos:

Se identificaron 9 familias con casos esporádicos de LQTS.
Se llevó a cabo el cribado de mutaciones (polimorfismo y secuenciación conformacional de un solo hilo) en probandos y miembros de la familia.
Se analizan los datos clínicos y los resultados de las pruebas genéticas para identificar a los portadores y determinar la penetración.

Principales resultados:

Se identificaron 15 (33%) portadores de genes asintomáticos entre 46 miembros de la familia.
Se determinó una tasa de penetración LQTS del 25% en estas familias.
Se encontró que los criterios de diagnóstico clínico tenían solo un 38% de sensibilidad en la identificación de portadores.

Conclusiones:

Los LQTS pueden exhibir una penetración muy baja, y muchos individuos son portadores de genes silenciosos.
Los portadores asintomáticos corren el riesgo de tener descendencia afectada y desarrollar torsades de pointes.
Se recomienda el cribado molecular de todos los miembros de la familia de pacientes con genotipo LQTS.

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