CMT 1A: Clinical Implications of Peripheral Myelin Protein 22 for Nerve Compress

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J Reconstr Microsurg. 2010 Oct 25

Clinical Implications of Peripheral Myelin Protein 22 for Nerve Compression and

Neural Regeneration: A Review.

Hui-Chou HG, Hashemi SS, Hoke A, Dellon AL.

Division of Plastic and Reconstructive Surgery, s Hopkins/University of

land Plastic Surgery Program, Baltimore.

Abstract

Peripheral myelin protein 22 (PMP22) is a major component of the peripheral

myelin sheath. The PMP22 gene is located on chromosome 17p11.2, and defects in

PMP22 gene have been implicated in several common inherited peripheral

neuropathies. Hereditary neuropathy with liability to pressure palsies (HNPP),

Charcot-Marie Tooth disease type 1A (CMT1A), Dejerine-Sottas syndrome, and

congenital hypomyelinating neuropathy are all associated with defects in PMP22

gene.

The disease phenotypes mirror the range of expression of PMP22 due to the

corresponding genetic defect. HNPP, characterized by a milder recurrent episodic

focal demyelinating neuropathy, is attributed to a deletion leading to PMP22

underexpression.

On the other end of the spectrum, CMT1A leads to a more uniform demyelination

and axonal loss, resulting in severe progressive distal weakness and

paresthesias; it is due to a duplication at 17p11.2 leading to PMP22

overexpression. Additional point mutations result in varying phenotypes due to

dysfunction of the resultant PMP22 protein.

All inherited neuropathies are diagnosed with a combination of physical findings

on examination, electromyography, sural nerve biopsies, and genetic testing.

Treatment and management of these disorders differ depending on the underlying

genetic defect, nerves involved, and resulting functional impairments. A review

of current literature elucidates clinical, microsurgical implications, and

management of patients with PMP22-related neuropathy.