RESUMO
Waardenburg syndrome (WS) is a rare disorder comprising sensorineural deafness and pigmentation abnormalities. Four distinct subtypes are defined based on the presence or absence of additional symptoms. Mutations in six genes have been described in WS. SOX10 mutations are usually associated with a more severe phenotype of WS with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, and Hirschsprung disease. Here we report a 32-year-old man with a novel heterozygous missense variant in SOX10 gene, who presented with congenital deafness, Hirschsprung disease, iris heterochromia, foot deformity, and intermediate conduction velocity length-dependent sensorimotor neuropathy. This case highlights that the presence of other non-neuropathic features in a patient with presumed hereditary neuropathy should alert the clinician to possible atypical rare causes.
Assuntos
Mutação/genética , Fatores de Transcrição SOXE/genética , Síndrome de Waardenburg/genética , Adulto , Cistos Aracnóideos/complicações , Cistos Aracnóideos/diagnóstico por imagem , Atrofia/diagnóstico por imagem , Atrofia/etiologia , Cerebelo/diagnóstico por imagem , Análise Mutacional de DNA , Doença de Hirschsprung/etiologia , Humanos , Doenças da Íris/etiologia , Imageamento por Ressonância Magnética , Masculino , Condução Nervosa/genética , Transtornos da Pigmentação/etiologia , Síndrome de Waardenburg/diagnóstico por imagem , Síndrome de Waardenburg/fisiopatologiaRESUMO
X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.