Charcot–Marie–Tooth with pyramidal signs is genetically heterogeneous: Families with and without <i>MFN2</i> mutations

Abstract

Charcot–Marie–Tooth neuropathy (CMT) is divided into two broad categories: demyelinating forms (CMT1), characterized by median motor conduction velocities of <38 m/s; and axonal forms (CMT2), characterized by axonal degeneration without demyelination and preserved or only mildly reduced motor conduction velocities.1 CMT with pyramidal features is an axonal form of CMT with variable pyramidal features (upper motor neuron signs) but without frank spasticity. The dominantly inherited form was classified as hereditary motor and sensory neuropathy type V (HMSN V [MIM 600361])2 and also defined as peroneal muscular atrophy with pyramidal features.3 The pyramidal signs include extensor plantar responses, mild increase in tone, flexor plantar weakness, and preserved or increased reflexes (knee and ankle). There is no frank spasticity differentiating this disorder from the spastic paraplegias. The disorder has not been mapped to a chromosomal locus. Eight loci have been reported for the autosomal dominant forms of CMT2. Genes with mutations have been identified for five of these loci. Recently, two closely mapped genes, MFN2 (MIM 608507) and KIF1B (MIM 6059950), were reported to cause CMT2A4,5, but mutations in KIF1B have not been independently …