Charcot-Marie-Tooth neuropathy type 4 (CMT4) is a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Affected individuals have the typical CMT phenotype of distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity.
The diagnosis of CMT4 subtypes is based on clinical, pathologic, and genetic criteria. The genes associated with nine CMT4 subtypes have been identified: GDAP1 (CMT4A), MTMR2 (CMT4B1), CMT4B2 (SBF2), SH3TC2 (CMT4C), NDRG1 (CMT4D), EGR2 (CMT4E), PRX (CMT4F), FGD4 (CMT4H), and FIG4 (CMT4J). Molecular genetic testing for all of these genes is available on a clinical basis.
The CMT4 subtypes are inherited in an autosomal recessive manner. Parents of an affected individual are obligate carriers of the CMT4-related gene mutation present in their family. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in an affected family member are known.