RESUMO
Facial-onset sensory and motor neuronopathy (FOSMN) syndrome represents a rare, slowly progressive, lower motor neuron disease with sensory compromise, involving mainly the face, bulbar region and upper limbs. However, non-motor symptoms and neurogenetic studies have rarely been evaluated in large case series. In the present study, 10 unrelated Brazilian patients with FOSMN syndrome underwent extensive clinical, laboratory, neurophysiological and neurogenetic assessment. Median age at symptom onset was 52.1 years, and men and women were equally affected. Patients presented with hemifacial or bilateral facial paresthesia and weakness, which evolved with dysphagia, dysphonia, and facial and tongue atrophy and, finally, a dropped-head, upper limb weakness and syringomyelia-like sensory disturbances in the upper limbs. All 10 patients showed chronic diffuse neurogenic compromise of bulbar, cervical and thoracic myotomes, and abnormal blink reflex tests. A positive family history of neurodegeneration was identified in six cases, and revealed pathogenic gene variants in three families (involving VCP, TARDBP and CHCHD10). Thus, our case series has revealed new findings regarding FOSMN syndrome: (i) its clinical course is not always benign, with poorer prognoses associated with dropped-head syndrome and early bulbar compromise; (ii) FOSMN syndrome may be part of a complex familial neurodegenerative spectrum; and (iii) a definite genetic basis may be observed in some cases.
Assuntos
Doenças do Nervo Facial/fisiopatologia , Doença dos Neurônios Motores/fisiopatologia , Adulto , Idade de Início , Idoso , Piscadela , Brasil , Doenças do Nervo Facial/diagnóstico por imagem , Doenças do Nervo Facial/genética , Feminino , Testes Genéticos , Transtornos Heredodegenerativos do Sistema Nervoso/epidemiologia , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/diagnóstico por imagem , Doença dos Neurônios Motores/genética , Debilidade Muscular/etiologia , Atrofia Muscular Espinal/epidemiologia , Neuroimagem , Exame Neurológico , Parestesia/etiologiaRESUMO
The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.