Talia L Varley1, Pierre R Bourque2, Steven K Baker1. 1. Department of Medicine, Neuromuscular Disease Clinic, McMaster University, Hamilton, HSC Room 2H22, 1200 Main Street West, Ontario, Canada, L8N 3Z5. 2. Division of Neurology, University of Ottawa, Ottawa, Ontario, Canada.
Abstract
INTRODUCTION: Charcot-Marie-Tooth type 4C (CMT4C) is an autosomal recessive dysmyelinating neuropathy characterized by precocious and rapidly progressive scoliosis. METHODS: Patients in a French-Canadian kindred were evaluated with clinical examination, electrophysiologic study, and genomic DNA extraction. RESULTS: Six of 10 siblings were clinically symptomatic with supportive electrophysiologic features. The proband presented with regional side-to-side sensorimotor asymmetry, typical pes cavus without obvious scoliosis, and unremarkable plain films of the spine. Affected siblings all share symptoms of foot deformity but have variable onset of neuropathic symptoms, degree of extremity weakness, progression of symptoms, and, most notably, evidence of scoliosis. DNA sequence analysis revealed a novel combination of 2 known recessive mutations, p.R904X and p.R954X, in the SH3TC2 gene. CONCLUSIONS: A broad spectrum of phenotypes should be considered in the possible diagnosis of CMT4C. The absence of scoliosis or late-onset symptoms should not exclude SH3TC2 from the list of candidate genes under consideration. Age of onset and clinical features were variable and suggest that polygenic factors contribute to the final phenotype.
INTRODUCTION:Charcot-Marie-Tooth type 4C (CMT4C) is an autosomal recessive dysmyelinating neuropathy characterized by precocious and rapidly progressive scoliosis. METHODS:Patients in a French-Canadian kindred were evaluated with clinical examination, electrophysiologic study, and genomic DNA extraction. RESULTS: Six of 10 siblings were clinically symptomatic with supportive electrophysiologic features. The proband presented with regional side-to-side sensorimotor asymmetry, typical pes cavus without obvious scoliosis, and unremarkable plain films of the spine. Affected siblings all share symptoms of foot deformity but have variable onset of neuropathic symptoms, degree of extremity weakness, progression of symptoms, and, most notably, evidence of scoliosis. DNA sequence analysis revealed a novel combination of 2 known recessive mutations, p.R904X and p.R954X, in the SH3TC2 gene. CONCLUSIONS: A broad spectrum of phenotypes should be considered in the possible diagnosis of CMT4C. The absence of scoliosis or late-onset symptoms should not exclude SH3TC2 from the list of candidate genes under consideration. Age of onset and clinical features were variable and suggest that polygenic factors contribute to the final phenotype.
Authors: Nivedita U Jerath; Ami Mankodi; Thomas O Crawford; Christopher Grunseich; Hasna Baloui; Chioma Nnamdi-Emeratom; Alice B Schindler; Terry Heiman-Patterson; Roman Chrast; Michael E Shy Journal: Muscle Nerve Date: 2017-10-24 Impact factor: 3.217
Authors: Kayla M D Cornett; Manoj P Menezes; Paula Bray; Mark Halaki; Rosemary R Shy; Sabrina W Yum; Timothy Estilow; Isabella Moroni; Maria Foscan; Emanuela Pagliano; Davide Pareyson; Matilde Laurá; Trupti Bhandari; Francesco Muntoni; Mary M Reilly; Richard S Finkel; Janet Sowden; Katy J Eichinger; David N Herrmann; Michael E Shy; Joshua Burns Journal: JAMA Neurol Date: 2016-06-01 Impact factor: 18.302