Charcot-Marie-Tooth hereditary neuropathy type 2 (CMT2) is an axonal (non-demyelinating) peripheral neuropathy characterized by distal muscle weakness and atrophy, mild sensory loss, and normal or near-normal nerve conduction velocities. CMT2 is clinically similar to CMT1, although typically less severe. Peripheral nerves are not enlarged or hypertrophic. The subtypes of CMT2 are similar clinically and distinguished only by molecular genetic findings.
The diagnosis is based on clinical findings and EMG/NCV characteristics. The 15 genes in which mutations are known to cause CMT2 subtypes are KIF1B (CMT2A1), MFN2 (CMT2A2), RAB7A (formerly RAB7) (CMT2B), LMNA (CMT2B1), MED25 (CMT2B2), TRPV4 (CMTC), GARS (CMT2D), NEFL (CMT2E/1F), HSPB1 (CMT2F), MPZ (CMT2I/J), GDAP1 (CMT2H/K), HSPB8 (CMT2L), AARS (CMT2N), DYNC1H1 (CMT2O), and LRSAM1 (CMT2P). Molecular genetic testing is clinically available for CMT subtypes 2A1, 2A2, 2B, 2B1, 2B2, 2C, 2D, 2E, 2F, 2I, 2J, 2H/K, 2L, 2N, 2O, and 2P.
CMT2B1, CMT2B2, and CMT2H/K are inherited in an autosomal recessive manner; all other subtypes of CMT2 are inherited in an autosomal dominant manner. Most probands with autosomal dominant subtypes of CMT2 have inherited the disease-causing mutation from an affected parent. The offspring of an affected individual with autosomal dominant CMT2 are at a 50% risk of inheriting the altered gene. Availability of prenatal diagnosis varies by subtype.