Connexin 32 (Cx32) is a gap junction protein expressed in the peripheral nervous system (PNS), central nervous system (CNS), and in many other tissues.1 Mutations in the Cx32 gene are associated with X-linked Charcot-Marie-Tooth disease (CMTX) , and account for about 10% of the patients with hereditary motor and sensory neuropathy (HMSN).

At least 130 different mutations have been reported in the Cx32 gene causing peripheral neuropathy. Classically, distal weakness and atrophy initially involving the lower limbs, as well as sensory abnormalities, depressed tendon reflexes, and pes cavus are usually found in males by the second decade, whereas in carrier females clinical manifestations, if present, are in most instances milder than in affected males. Nerve conduction studies in affected males are usually, but not always, suggestive of a demyelinating process, although they are not quite as slow as in patients with CMT1A. In females, conduction velocities (CVs) may be in the normal range or only mildly reduced, as seen in axonal neuropathies.

We describe a new Cx32 point mutation (Ala³⁹ to Val) in genetically established identical twins with similar CMT phenotypes and extensor plantar reflexes.

The probands were first seen at the age of 20. Their principal complaint was cramps in the legs, “going over” on the ankles, and mild weakness in the hands. On examination, Twin 1 could not stand on his heels and …