Charcot-Marie-Tooth disease: frequency of genetic subtypes in a German neuromuscular center population

Abstract

Charcot-Marie-Tooth (CMT) neuropathies belong to the most common neurogenetic disorders. To date, mutations in more than 40 genes are known to be able to cause CMT. This genetic heterogeneity is a challenge for genetic diagnostics. Data on frequencies of mutations in CMT genes from large patient cohorts are needed to develop strategies for efficient genetic testing. In this study we have analysed patient histories, electrophysiological and genetic testing data in our cohort of 776 patients. In electrophysiologically demyelinating CMT, PMP22 duplication was the most common genetic cause, followed by mutations in GJB1 and MPZ. In axonal CMT, GJB1 was the most commonly affected gene, followed by MFN2 and MPZ. In CMT1, the clearance rate was 66%, in CMT2 it was 35%. Overall, the genetic clearance rate in our patient cohort was 58%. We found a higher rate of genetic diagnosis in patients seen in our neuromuscular center compared to out-of-clinic patients whose DNA was tested in our laboratory. This study provides further data on frequencies of CMT genes and subtypes and points to the importance of a thorough clinical and electrophysiological work-up for the direction of genetic testing.

Keywords: Charcot-Marie-Tooth; Genetics; Hereditary neuropathy; Neuromuscular; Peripheral neuropathy.