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Hereditary Motor and Sensory Neuropathy Type 2, HMSN2, CMT2A2 (axonal) - MFN2

Clinical Features

The clinical features of Axonal Hereditary Motor and Sensory Neuropathy Type 2 (HMSN2, CMT2A2) belong to those of classic HMSN. Age of onset and progression of the disease can vary greatly, even within one family, and a clinical or electrophysiological history of the disease in the family need not be present. This primarily axonal neuropathy progresses slowly and normally begins in childhood or adolescence with distal paresis and atrophy in the lower extremities.

In contrast to HMSN1, sensibility often remains unaffected and motor nerve conduction velocities show only minor delay (> 40m/s), if any. Optic atrophy and/or loss of vision can also occur and, in some cases, subside; due to the presence of these additional symptoms, the disease is also classified as HMSN Type 6.

Genetic Information

CMT2A follows an autosomal dominant pattern of inheritance and is caused by mutations in the MFN2 gene (Mitofusin 2) located on chromosome 1p36.2. The gene consists of 17 coding exons.

Prevalence

MFN2 mutations are found in 10-20% of patients with axonal CMT neuropathy, thus representing the most common cause of the axonal form of HMSN.

Diagnostic