Genetics of Hereditary Neuropathies

Abstract

Hereditary motor and sensory neuropathies (HMSN) have been previously classified on the basis of clinical course, mode of inheritance and neuropathological findings [1]. In the past years, considerable advances in the knowledge of this heterogeneous group of disorders have been made due to genetic studies demonstrating that duplication, deletion or mutation of specific genes of the peripheral myelin are the most common causes of HMSN. The classification of HMSN and of related disorders, from now forward called with the eponymous Charcot-Marie-Tooth disease (CMT), is continuously evolving. CMT has a prevalence of 1 case every 2500 [1] and is divided into CMT1 and CMT2 according to neurophysio-logic and neuropathologic findings. In fact, in CMT1 the motor nerve conduction velocity (MNCV) of the median nerve is 38 m/s) and sural nerve biopsy shows signs of primary axonal involvement with minimal signs of myelin sufferance. CMT1 and CMT2 are usually inherited as dominant disorders and are clinically indistinguishable. A severe form of CMT called Dejerine-Sottas syndrome (DSS) has onset in early childhood and a progressive and disabling clinical course.