Overview of Charcot-Marie-Tooth disease type 1A.
Type 1A CMT disease is most commonly due to a segmental duplication on chromosome 17p11.2, leading to the presence of an extra copy of the gene for peripheral myelin protein 22 (PMP22). Inheritance is autosomal dominant in pattern. Analysis of nerve biopsies suggests that the disorder is caused by increased gene dosage. Occasionally CMTIA results from point mutations in the PMP22 gene. Onset of symptoms in cases with a duplication is usually in the first decade of life; slowing of nerve conduction velocity is evident from the age of 2 years. Active demyelination is restricted to childhood. It leads to hypertrophic "onion bulb" changes and is accompanied and followed by progressive axonal loss. The commonest clinical phenotype is the CMT syndrome with distal muscle wasting and weakness, tendon areflexia, usually mild sensory loss, and foot deformity. Other phenotypes include the Roussy-Lévy syndrome, in which postural tremor and ataxia are associated, and cases with severe distal sensory loss and acrodystrophic changes.
Thomas
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Department of Clinical Neurosciences, Royal Free and University College Medical School, London, United Kingdom.
D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17; D020440:Gene Duplication; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics; D017354:Point Mutation
D009185:Myelin Proteins; C073687:PMP22 protein, human