Autosomal dominant inherited HNPP is a recurrent motor and sensory neuropathy in a single nerve, with onset in early adulthood although rarely before the age of 20. After prolonged compression of a nerve, e.g., after prolonged kneeling, patients experience attacks of paresthesia (such as tingling and numbness) in the specific area supplied by the affected nerve branch (mononeuropathy, such as carpal tunnel syndrome, peroneal paralysis with weakness of ankle dorsiflexion). In 50% of the cases, the symptoms disappear completely after a few days. In similar unrelated traumas, the pressure paresis may reoccur. The extent of the impairment is comparatively mild and there is no reduction in life expectancy. Both symptomatic and asymptomatic patients show an extension of the distal nerve conduction latencies in the electrophysiological examination. The nerve biopsy reveals demyelination and focal “sausage‑like” enlargements of the nerve (tomacula).
In 80% of the patients a 1.5 Mb large deletion is detectable in the chromosome region 17p11.2, which includes the PMP22 gene. This so-called “HNPP deletion” occurs de novo in 20% of cases. Pathogenic variants or minor deletions in the PMP22 gene are also found in 20% of patients.
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