Hereditary neuropathy with liability to pressure palsies, HNPP - PMP22

Tomaculous neuropathy

Klinische Symptomatik

Symptoms of a hereditary neuropathy with liability to pressure palsies (HNPP) vary widely, ranging from a mild numbness in the limbs to the severity of a HMSN type 1:

• Peripheral nerves are more sensitive for mild traumas
• Recovery within days to weeks
• Recurrent pressure palsies following similar trauma
• Nerve conduction velocity may be focally reduced accompanied by conduction block
• Clinically, HNPP may resemble HMSN1
• Carpaltunnel-syndrome may be caused HNPP

Genetik

About 80% of patients with a clinically diagnosed HNPP carry a reciprocal deletion of 1,4 Mb in the CMT1A-/HNPP-region located on chromosome 17p12, which includes the Peripheral Myelin Protein 22 (PMP22) gene. The resulting reduced PMP22 expression leads to a tomaculous neuropathy.
HNPP deletions follow an autosomal dominant pattern of inheritance, but may also occur de novo due to unequal crossing-over. Partial deletions result in asymmetric, late onset and focal neuropathies. Less frequently, a point mutation of PMP22 itself may be the cause. Mutations in the Myelin Protein Zero (MPZ) and Connexin 32 (Cx32) genes may result in similar neuropathies.
The most frequent Hereditary motor and sensory neuropathy type IA (HMSN1A) is caused by a CMT1A duplication of the identical 1,4 Mb region.

Häufigkeit

App. 1 : 5 000

 

Diagnostik