Inherited Neuropathies: Clinical, Genetic, and Biological Features

Neuropathy is a frequent component of numerous inherited syndromes. It is called Charcot-Marie-Tooth disease (CMT), when in isolation. The biology of axons and myelinating Schwann cells makes them vulnerable to the effects of mutations in a large number of genes. This chapter emphasizes on the varieties of inherited demyelinating neuropathies, their clinical phenotypes, the mutations that cause these phenotypes, and update their pathogenesis gene-by-gene. The genetic classification of the nonsyndromic inherited neuropathies is also provided. Inherited neuropathies are usually caused by mutations in genes that are expressed by myelinating Schwann cells or neurons, which is the biological basis for the long-standing distinction between primary "demyelinating" and "axonal" neuropathies. Neuropathies can be isolated, the primary manifestation of a more complex syndrome, or overshadowed by other aspects of the inherited disease. Increasing knowledge of the molecular genetics causes of inherited neuropathies facilitates a faster and more accurate diagnosis, setting the stage for the development of specific therapeutic interventions.