From the Research
Definition and Prevalence of Charcot-Marie-Tooth Disease
- Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited disorders affecting the peripheral nervous system, with a prevalence of 1/2500 1, 2.
- It is one of the most common inherited neuropathies, often presenting during childhood 3.
- CMTs are differently classified according to the age of onset, type of inheritance, and type of inheritance plus clinical features 4.
Clinical Manifestations
- The common clinical manifestations of the disease are distal muscle weakness and atrophy, often associated with a characteristic steppage gait and foot deformities 5.
- Transient acute and recurrent or chronic central nervous system manifestations, predominantly, dysarthria, dysphagia, motor weakness, and ataxia, have been recognized as a feature of the X-linked type 1 of CMT (CMTX1) 5.
- CMT can also manifest with motor and sensory dysfunctions of the peripheral nervous system, mainly starting with slow progressive weakness of the lower extremities 4.
Genetic Basis
- Mutations in more than 80 genes have been identified as causing either demyelinating forms (CMT1) or axonal forms (CMT2) of the disease 1.
- More than 100 genes have been implicated as causal factors for CMT, with mutations in the PMP22 being one of the most common 4.
- Concomitant variant mutations in CMTs have been uncommonly reported, with examples including mutations in the MPZ and MFN2 genes 4.