RESUMEN
OBJECTIVE: To assess vestibular function in patients with familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy - caused by a mutation in the IKBKAP gene (c.2204â¯+â¯6â¯T>C) - and characterized by marked gait ataxia. METHODS: Cervical and vestibular evoked myogenic potentials (cVEMPs and oVEMPs) were recorded from the sternocleidomastoid (SCM) and extraocular muscles in 14 homozygous patients, 2 heterozygous patients, and 15 healthy controls during percussion of the forehead. RESULTS: cVEMP and oVEMP amplitudes were significantly lower, and peak latencies significantly delayed, in the FD patients. There were no differences in overall EMG during attempted maximal voluntary contractions of the SCM muscle, suggesting intact efferent function. The two heterozygotes with a minor haplotype missense (R696P) mutation in exon 19 of the IKBKAP gene had cVEMP responses less affected than the homozygous. CONCLUSIONS: The founder mutation in the IKBKAP gene affects the development of vestibular afferent pathways, leading to attenuated cVEMPs. SIGNIFICANCE: Vestibular abnormalities may contribute to the gait ataxia in FD.
Asunto(s)
Proteínas Portadoras/genética , Disautonomía Familiar/genética , Predisposición Genética a la Enfermedad , Mutación , Enfermedades Vestibulares/genética , Potenciales Vestibulares Miogénicos Evocados/fisiología , Adolescente , Adulto , Disautonomía Familiar/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Factores de Elongación Transcripcional , Enfermedades Vestibulares/fisiopatología , Adulto JovenRESUMEN
We reviewed the charts of all patients with familial dysautonomia (n = 631) and found that 2% had been diagnosed with tumors. We hypothesize that the IkappaB Kinase-associated protein gene mutation, which causes aberrant RNA splicing in patients with familial dysautonomia, may contribute to tumorigenesis in this genetically homogenous patient population.
Asunto(s)
Disautonomía Familiar/patología , Síndromes Neoplásicos Hereditarios/epidemiología , Síndromes Neoplásicos Hereditarios/patología , Adolescente , Adulto , Proteínas Portadoras/genética , Niño , Estudios de Cohortes , Bases de Datos Factuales , Disautonomía Familiar/genética , Disautonomía Familiar/mortalidad , Femenino , Humanos , Israel , Judíos/genética , Masculino , Persona de Mediana Edad , Síndromes Neoplásicos Hereditarios/genética , Estudios Retrospectivos , Factores de Elongación Transcripcional , Estados Unidos , Adulto JovenRESUMEN
A historical perspective of familial dysautonomia is presented, highlighting the early contributions of Dr. Joseph Dancis. As further investigations proceeded, his original observations have withstood the test of time and may contribute to determining the molecular abnormality in this rare genetic disorder. Dr. Dancis's work in this area serves as a model of how observations based on clinical acumen and critical thinking can be verified by future technological advances.