Experiencia en el diagnóstico, pesquisa en cascada y manejo multidisciplinario de pacientes con síndrome X frágil / Experience in diagnosis, cascade screening and multidisciplinary management of patients with fragile X syndrome

RESUMEN

Resumen. El Síndrome X Frágil (SXF) constituye la causa más frecuente de retraso mental hereditario y autismo. Los individuos con mutación completa (MC) presentan alteraciones clínicas que incluyen déficit cognitivo y atencional, hiperactividad, autismo y problemas emocionales. Los portadores de premutación (PM) pueden afectarse del síndrome de temblor y ataxia asociado a X frágil (FXTAS); el 30 por ciento de las mujeres con PM presentan insuficiencia ovárica prematura(FXPOI). Cuando un individuo presenta una MC es frecuente encontrar otros familiares afectados. El fenotipo al nacer no es evidente, se sugiere que debe hacerse el diagnóstico entre los35-37 meses, sin embargo, la edad de diagnóstico en Chile es en promedio de 8 +/- 5.8 años. El centro de diagnóstico, tratamiento y seguimiento de pacientes con síndrome X frágil (CDTSXF)es un centro multidisciplinario, que incluye diagnósticos moleculares, genetistas médicos, asesoramiento genético, neurólogos, terapeutas ocupacionales, fonoaudiólogo, evaluaciones nutricionales y psicológicas para las familias afectadas. Desde el año 2010 hemos asistido a 28familias y detectado un número significativo de afectados debido a la detección en cascada. Se ha diagnosticado a 63 probandos, 57 MC y ocho mosaicos de MC/PM. Entre las madres portadoras 37 son PM y dos presentaron una MC. En 9/28 familias había un adulto mayor con FXTAS, diez familias presentaron mujeres con FXPOI. 41/63 probandos han participado denle el protocolo multidisciplinario del CDTSXF. Los resultados de este enfoque multidisciplinario nos motiva a seguir trabajando en mejorar el comportamiento y desarrollo cognitivo de los pacientes y atender las principales necesidades de las familias afectadas.

ABSTRACT

Fragile X Syndrome (FXS) is the most common inherited form of mental retardation and a leading known cause of autism. Individuals with a full mutation (FM) present disabilities including cognitive and attention deficit, hyperactivity, autism, and other emotional problems. Carriers of a premutation (PM) may be affected by fragile X associated tremor/ataxia syndrome (FXTAS) and primary ovarian insufficiency (FXPOI) in 30 percent of PM women. Therefore, multigenerational family involvement is commonly found when a proband is diagnosed with a FXS mutation. FXS has no obvious phenotype at birth, it is suggested that the diagnosis should be made at 35-37 months; the age of diagnosis in Chile is on average 8+/-5.8 yo. The center for diagnosis, treatment and monitoring of patients with fragile X syndrome (CDTTRABAJOMFXS), is a multidisciplinary center that includes molecular testing, medical geneticists, genetic counseling, neurologists, occupational therapists, physical therapists, and nutritional and psychological interventions to families with an FM proband. Since 2010, we have assisted 28 families with a total of 63 diagnosed probands using specific PCR and Southern blot tests. Among them, 57 had a FM and eight had a mosaic FM/PM. Among the mothers 37 are PM carriers and two presented a FM. An older adult with FXTAS was present in 9/28 families; ten families presented women with FXPOI. A significant number of affected family members have been detected through cascade screening. Among the probands 41 of 63 have received some of the multidisciplinary diagnostic and interventions. The results of this multidisciplinary work allow us to put forward more effort towards improving behavior and cognitive development of patients as well as trying to solve families’ main needs.