RESUMO
INTRODUCTION: The first episode of hereditary neuropathy with liability to pressure palsy (HNPP) in childhood is rare. METHODS: We analyzed retrospectively the data of 7 patients with a deletion in PMP22 and onset of symptoms before age 18 years. Direct sequencing of the LITAF (lipopolysaccharide-induced tumor necrosis factor) gene was performed in patients and family members. RESULTS: Clinical presentations varied from mononeuropathies to brachial plexopathy, with recurrent episodes in 4 patients. Electrophysiological abnormalities characteristic for HNNP were found in most subjects. Analysis of the LITAF gene revealed an Ile92Val polymorphism in 6 of 7 (86%) probands and 5 of 7 (83%) family members, over 4 times greater frequency than in the general population. CONCLUSIONS: Clinical suspicion of HNPP even when nerve conduction study results do not fulfill HNPP criteria should indicate genetic testing. In our patients, early-onset HNPP was associated frequently with isoleucine92valine LITAF polymorphism.
Assuntos
Artrogripose/genética , Artrogripose/fisiopatologia , Neuropatia Hereditária Motora e Sensorial/genética , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Condução Nervosa/fisiologia , Proteínas Nucleares/genética , Polimorfismo Genético/genética , Fatores de Transcrição/genética , Adolescente , Fatores Etários , Idade de Início , Artrogripose/diagnóstico , Criança , Pré-Escolar , Eletrofisiologia/métodos , Feminino , Deleção de Genes , Predisposição Genética para Doença/genética , Testes Genéticos , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Humanos , Masculino , Proteínas da Mielina/genética , Estudos RetrospectivosRESUMO
Charcot-Marie-Tooth type 1C disease (CMT1C) is a rare form of hereditary demyelinating neuropathy caused by mutations in the LITAF (lipopolysaccharide-induced tumor necrosis factor-ï¡) gene. CMT1C disease was mapped to chromosome 16p12-p 13.3. To date only a few mutations in the LITAF gene have been reported. Due to a small group of CMT1C reported patients, the phenotype of CMT1C is poorly characterized. CMT1C disease is a pure demyelinating neuropathy limited to the peripheral nervous system with a mild clinical course, manifesting without any additional symptoms. To the best of our knowledge, in this study, for the first time we present a three generational CMT1C family in which in the proband, CMT1C disease coexists with central demyelination fulfilling criteria of primary progressive multiple sclerosis (PPMS). The coexistence of PPMS and CMT1C in one family may not result from a common pathogenetic trait, however only in the proband with central demyelination and CMT1C we have detected a -308G>A sequence variant in the promoter of the TNF-α gene.