Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Hereditary Neuropathy with Liability to Pressure Palsy (Tomaculous Neuropathy, HNPP) [G60.9]

OMIM numbers: 162500, 601097 (PMP22)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh

Scientific Background

Autosomal dominant HNPP is a recurring, motor and sensory neuropathy in a single nerve. Onset is in early adulthood, rarely before 20 years of age. After prolonged compression of a nerve, e.g. after a longer period of kneeling, patients experience attacks of paresthesia (tingling, numbness) in the particular area supplied by the affected nerve (mononeuropathy, such as carpal tunnel syndrome, peroneal nerve damage with neuropathic gait). About 50% of all patients are free of signs and symptoms after a few days; pressure paresis reoccurs after similar, inadequate traumata. Patients are only mildly impaired; life expectancy is not reduced. Both symptomatic and asymptomatic patients show prolonged distal latency during electrophysiological examination. Nerve biopsy shows demyelination and focal thickening of the myelin sheath (tomacula).

A deletion 1.5 Mb of size is found in 80% of all patients in the chromosome region 17p11.2. This deletion includes the PMP22 gene, among others. In 20% of all cases the deletion, also known as “HNPP deletion”, occurs de novo. Point mutations or smaller deletions in the PMP22 gene are found in 22% of all patients.