The hereditary peripheral neuropathies have been classified based upon clinical characteristics, mode of inheritance, electrophysiologic features, metabolic defect, and specific genetic markers. The primary hereditary neuropathies predominantly affect peripheral nerves and produce symptoms of peripheral nerve dysfunction.
Historically, the primary hereditary neuropathies were designated by eponyms that had the connotation of specific clinical features (eg, Charcot-Marie-Tooth disease [CMT] or Dejerine-Sottas disease). However, phenotypic variability resulted in substantial diagnostic confusion.
The Dyck classification developed in the 1970s helped to define specific types based upon clinical and electrophysiologic features . Many of the primary hereditary neuropathies were divided into motor-sensory and sensory–autonomic neuropathies.
The primary hereditary motor sensory neuropathies (HMSN) are reviewed here. The primary hereditary sensory autonomic neuropathies (HSAN), the neuropathies not included in this classification, and the disorders affecting both the central and peripheral nervous systems are discussed separately. (See "Overview of hereditary neuropathies" and "Hereditary sensory and autonomic neuropathies" and "Hereditary neuropathies associated with generalized disorders".)
Hereditary motor sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth (CMT) disease, is really a spectrum of disorders caused by a specific mutation in one of several myelin genes that result in defects in myelin structure, maintenance, and formation. Each gene locus serves a specific function in maintaining myelin integrity. Gene expression can be altered by intragenic mutation but also by "gene dosage imbalance" caused by DNA duplications or deletions [2,3]. Duplication of the PMP22 gene causes CMT1A, the most common type of hereditary motor sensory neuropathy (~40 percent overall).