Charcot–Marie–Tooth disease type 2C: a distinct genetic entity. Clinical and molecular characterization of the first European family

Abstract

Charcot–Marie–Tooth disease type 2 is clinically and genetically heterogeneous. A particular clinical subtype of autosomal dominant Charcot–Marie–Tooth disease type 2, characterized by diaphragm and vocal cord paralysis, is labelled Charcot–Marie–Tooth disease type 2C but no genetic locus has been mapped for this form. We describe the first European family affected by Charcot–Marie–Tooth disease type 2C. Genetic analysis excluded linkage to locus of Charcot–Marie–Tooth disease type 2A, B, D, E and F, and to locus of distal hereditary motor neuronopathy type VII. In this family the disease has high penetrance, variable severity and apparently the most severe limb muscle involvement in the youngest generation. Vocal cord paralysis is unrelated to the degree of muscular weakness and patients with the most severe muscle involvement have absent or minimal respiratory symptoms. Charcot–Marie–Tooth disease type 2C is clinically and genetically different from Charcot–Marie–Tooth disease type 2A, B, D, E and F, and is not allelic with distal hereditary motor neuronopathy type VII.