Charcot-Marie-Tooth Neuropathy Type 1A (17p11.2)
Aliases: CMT1, CMT1A, Hereditary Motor and Sensory Neuropathy 1,HMSN1, Hereditary Neuropathy with liability to pressure palsies, HNPP
Gene(s) involved: PMP22 in the 17p11.2 critical region
Brief description of disorder: Charcot-Marie-Tooth Neuropathy Type 1A is a slowly progressive sensory and peripheral motor neuropathy characterized by distal muscle atrophy and weakness, slow nerve conduction, and sensory loss. Bilateral foot drop, pes cavus foot deformity, hip dysplasia, and absent or decreased tendon reflexes in the upper and lower extremities are common findings. Symptoms usually manifest between 5 and 25 years of age. Severity of disease is varied from asymptomatic to severe, with profound pain and disability.
The prevalence of CMT1A is estimated at 10 in every 100,000, however this may be understated.
Inheritance pattern: CMT1 is inherited in an autosomal dominant manner. Approximately one-third of all cases are reportedly a de novo chromosome abnormality.
Genetics: CMT1A is caused by a duplication of the PMP22 gene, located at 17p11.2. Of the Type I Charcot-Marie-Tooth Neuropathies, type 1A is the most common, representing more than 70% of all Charcot-Marie-Tooth Type 1 disorders. Duplications of PMP22 are present in 100% of affected individuals. Subtypes of CMT1 are clinically identical, therefore individuals who are negative for a PMP22 duplication should be considered for further molecular testing.
Test method at this facility: Conventional cytogenetic analysis, FISH and Array. Mutation analysis is not available at this facility for this disorder.
Test sensitivity: Cytogenetic analysis detects approximately 25% of deletions that are greater than 5Mb. FISH and array will detect 98-100% of duplications/ deletions. Duplications/ deletions that are smaller than 100kb will not be detected by array and duplications/ deletions smaller than the FISH probe will not be detected by FISH.
Specimen requirements for cytogenetic analysis, FISH, and array:
Adult: 3-5 ml peripheral blood in a sodium-heparin tube.
Newborn: 1-3 ml blood in a sodium-heparin tube.
Transport at room temperature.
Turn-around-time:
Newborns: 2-3 days
Non-STAT: 2-14 days
FISH: 6-8 days
Array: 5-14 days
References: GeneReviews
revised: 5-20-2011
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