Hereditary Motor and Sensory Neuropathy, CMT4C (Demyelinating) - SH3TC2

Klinische Symptomatik

Autosomal recessive Charcot-Marie-Tooth Neuropathy Type 4 is caused by mutations in the SH3TC2 gene. The clinical symptoms of autosomal recessive neuropathies are similar to those of the more common autosomal dominant forms. Typical signs of the disease are distal, progressive muscle weakness and atrophy, foot deformation and distal loss of sensibility. The age of onset is normally prior to age 10; the first manifestation is often delayed motor development. The severity of CMT4C neuropathy varies; the majority of patients develop severely pronounced scoliosis early on, as well as proximal muscle weakness. Motor nerve conduction velocities are usually delayed (22m/s on average).

Genetik

CMT4C follows an autosomal recessive pattern of inheritance. The gene SH3TC2 (KIAA1985) is located on chromosome 5q32 and consists of 17 coding exons.

Häufigkeit

SH3TC2 gene mutations are found in 20% of all patients with autosomal recessive CMT neuropathy. Two common founder mutations have been found in various ethnic groups (p.R954X) and/or in the Roma population (p.R1109X).

 

Diagnostik