Dados do Trabalho

Título

Clinical and electrophysiological features of a Brazilian cohort of Charcot-Marie-Tooth type 4C (CMT4C)

Resumo

Introduction: Charcot-Marie-Tooth (CMT) is a clinical and genetically heterogeneous group of inherited neuropathies with an estimated prevalence of 1 in 2500 individuals. CMT4 is a group of demyelinating neuropathy with autosomal recessive inheritance. To date, there are 11 causative genes. CMT4C is caused by pathogenic variants in SH3TC2. It usually presents in the first decade of life with distal muscle weakness, pes cavus, difficulty walking and slow nerve conduction velocities, additional features include scoliosis. Objective: We aim to describe the clinical and electrophysiological features of a case series of CMT4C from a tertiary Hospital. Methods: Clinical and electrophysiological data were retrospectively collected from clinical records. Seven patients from five different families with molecular diagnosis were included. Results: Four out seven were female. The most frequently presenting symptoms were frequent falls and imbalance (42,8%). In five patients symptoms started in the first decade. Other symptoms were described, as feet deformities, distal weakness, distal paresthesia, scoliosis, difficulty walking and difficulty to run. Deep tendon reflexes were absent or reduced throughout, and vibratory sensation was abnormal on the lower limb in all patients. Nerve conduction studies were characterized by patchy sensory and motor reduction of the conduction velocity with at least one nerve presenting with temporal dispersion (TD).
Conclusion: Biallelic pathogenic variants in the gene SH3TC2 are a known cause of demyelinating neuropathy, being the most common subtype of CMT4 in several populations. TD indicates desynchronization of components CMAP due to different rates of conduction. Recently, nerve pathology from SH3TC2-knockout animal models revealed loss of internodal architecture that could ultimately cause TD. Suggests an important role of this gene in peripheral nerve maintenance, which may be a frequent finding in patients with CMT4C that may differentiate it from other CMT subtypes.

Palavras Chave

Charcot-Marie-Tooth disease, autossomal recessivo CMT, CMT4C, SH3TC2

Área

Neurogenética