Hereditary Motor and Sensory Neuropathy - MPZ

Klinische Symptomatik

MPZ/P0 gene mutations can cause various forms of demyelinating or axonal autosomal dominant Charcot-Marie-Tooth (CMT) neuropathies. Depending on the genotype, the disease can lead to serious, life-threatening neuropathy in childhood, analogous to Dejerine-Sottas Neuropathy (DSN) or Congenital Hypomyelination Neuropathy (CHN) phenotypes. Another possibility is a milder progression of the disease which manifests itself in late childhood or in adulthood (CMT1B /HMSN1B, CMT2I, or CMT2J/HMSN2). Additional symptoms such as deafness and pupil anomalies (Argyll-Robertson pupils) have also been observed. In rare cases, symptoms are quite similar to a hereditary neuropathy with liability to pressure palsies (HNPP). With those forms developing in early childhood, nerve conduction velocities are often severely impaired; with late manifest forms, nerve conduction velocities are only mildly delayed, if not normal, and thus belong to the axonal forms of the disease.

Genetik

Forms of CMT associated with mutations in the MPZ gene follow an autosomal dominant pattern of inheritance. The Myelin Protein Zero (MPZ/PO) gene (6 coding exons) is located on chromosome 1 (1q22-33). MPZ accounts for the greatest number of myelin structure proteins in the peripheral nerves and is essential to myelin compaction.

Häufigkeit

MPZ gene mutations are found in approx. 5% of patients with an autosomal dominant demyelinating, axonal, or intermediate CMT neuropathy (CMT1 or 2) and represent the third most common genetic cause of this illness (the first two most common causes are mutations in the PMP22 and Cx32 genes).

 

Diagnostik