Charcot–Marie–Tooth disease type 4C in Norway: Clinical characteristics, mutation spectrum and minimum prevalence.

Highlights • Charcot–Marie–Tooth disease, type 4C is the most common recessive CMT in Norway. • We identified six new mutations in the SH3TC2-gene causing CMT4C. • Scoliosis, sensory ataxia and early debut were present in almost all CMT4C patients. • About 50% of CMT4C patients had proximal paresis and cranial nerve affection. Abstract Autosomal recessive Charcot–Marie–Tooth disease (CMT) is considered rare and phenotypic descriptions are scarce for the different subgroups. Mutations in the SH3TC2 gene, causing recessive demyelinating CMT type 4C have been found in several Norwegian CMT patients over the last years. We aimed to estimate a minimum prevalence and to study the genotypic and phenotypic variability of CMT4C in Norway. Patients were selected from diagnostic registries in medical genetic centers in Norway for cases of CMT4C. All patients were invited to complete a questionnaire and give medical consent to the use of clinical data from medical hospital records. A total of 35 patients from 31 families were found with CMT4C, which gives a minimum prevalence of 0.7/100,000 in Norway. Six new mutations were identified. Most patients had debut in the first decade with foot deformities, distal limb paresis, sensory ataxia and scoliosis. Proximal lower limb paresis and cranial nerve involvement was seen in about half of the patients. CMT4C is the most common recessive CMT in Norway. In addition to the classic distal limb affection, early debut, scoliosis, proximal paresis, cranial nerve affection and sensory ataxia are the most prominent features of CMT4C. [ABSTRACT FROM AUTHOR]