Hereditary motor and sensory neuropathies.

The hereditary motor and sensory neuropathies (HMSN) represent a genetically heterogeneous collection of disorders in which patients develop a progressive muscular atrophy and sensory neuropathy of the distal extremities. Although Dyck' has noted seven types, the best described of these are HMSN types I and II (Charcot-Marie-Tooth disease) and Dejerine-Sottas (DS) disease, HMSN III. In contrast to other neurological disorders, such as Huntington's disease and myotonic dystrophy, there appears to be extensive genetic diversity in HMSN. The recent use of pedigree linkage analysis together with recombinant DNA techniques in these disorders has finally begun to clarify this confusing group of diseases. Charcot and Marie,s and independently Tooth,6 described a hereditary progressive muscular atrophy of the lower extremities in 1886. The former authors suspected the disorder represented a myelopathy, while Tooth considered it to be a 'true neuropathy'. Today Charcot-Marie-Tooth (CMT) disease represents the most common inherited neuropathy, with estimates of 36/100 0007 for the prevalence of its most frequent type, the autosomal dominant form. Presentation of symptoms is commonly in childhood or as a young adult. Initial weakness occurs in a peroneal nerve distribution with development of the characteristic foot drop, pes cavus, and hammer toes. Sensory examination is abnormal as well, but deficits are usually not symptomatic. The disease is progressive and atrophy of the distal upper extremities may occur in many subjects. Like many inherited neuro-logical disorders, CMT is marked by variable expres-sivity. Some patients may have only minimal symptoms, and their diagnosis may rest on nerve conduction studies or obligate carrier status, while others may require extensive orthopaedic intervention to maintain ambulation. A few patients may become wheelchair dependent. Ataxia and especially intention tremor are not uncommon.8 Prominence of these later symptoms led Roussy and Levy9 to describe what was initially believed to be a distinct syndrome. However, subsequent identification of families in which the CMT1 (HMSN I) and Roussy-Levy phenotypes segregate as one gene has led to the conclusion that patients with Roussy-Levy syndrome actually represent extreme expressions of CMT1.'0 With the known linkages to chromosomes 17 and 1 in CMT1, proof of this clinical impression may be obtained through future linkage analysis. In 1968, Dyck and Lambert" 12 divided the autosomal dominant forms of CMT into two types, based on physiological and pathological criteria: (1) the demyelinating form, CMT1, with severely decreased nerve condition velocities (NCV) and hypertrophic changes on biopsy, and (2) CMT2, the …