Hereditary Motor and Sensory Neuropathy Type 1, HMSN1, CMT1A - PMP22

Klinische Symptomatik

HMSN typ 1 (CMT1A) is not only the most common neurogenic muscular atrophy, it is also a clinically and genetically heterogenous disorder of the peripheral nervous system:

• Slowly progressing, symmetric and demyelinating neuropathy
• Symmetric atrophies, pareses beginning in lower extremities
• Gradual development of pareses in the upper extremities
• Deep tendon reflexes frequently disappear prior to the appearance of pareses
• Dysaesthesia and vasomotoric impairment
• Nerve conduction velocitiy (NCV) N. medianus mot.< 38 m/s
• HMSN1 manifestation most frequently prior to 30 years of age

Genetik

Approximately 50 % of patients suffering from clinically diagnosed HMSN1 (CMT1) carry a 1.4Mb tandem duplication on the short arm of chromosome 17 (17p12), where the peripheral myelin protein 22 (PMP22) is found. The gene dosage alteration and over-expression of PMP22 causes HMSN1, classified as CMT1A. This CMT1A duplication follows an autosomal dominant pattern of inheritance and is caused by an unequal cross-over (possibly de novo). Point mutations in the PMP22 gene have been identified in rare cases. These mutations may be accompanied by hearing impairment and can be as severe as congenital hypomyelination.
Hereditary neuropathy with liability to pressure palsies (HNPP) is normally caused by a reciprocal deletion of the CMT1A region. The phenotype can be as severe as a HMSN 1 (see HNPP information). Carpaltunnel-syndrome may also be caused by an underlying HNPP/HMSN. Many more loci and genes are spread over the entire genome, affecting almost every chromosome (see introduction to HMSN) and are described in the respective sections on this website.

Häufigkeit

1 : 2 500 to 7 : 100 000

 

Diagnostik