Hereditary Neuropathy with Liability to Pressure Palsies

Clinical characteristics: Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by recurrent acute sensory and motor neuropathy in a single or multiple nerves. The most common initial manifestation is the acute onset of a non-painful focal sensory and motor neuropathy in a single nerve (mononeuropathy). The first attack usually occurs in the second or third decade but earlier onset is possible. Neuropathic pain is increasingly recognized as a common manifestation. Recovery from acute neuropathy is usually complete; when recovery is not complete, the resulting disability is mild. Some affected individuals also demonstrate a mild-to-moderate peripheral neuropathy.

Diagnosis/testing: The diagnosis of HNPP is established in a proband with suggestive clinical and electrophysiologic findings and either the 1.5-Mb recurrent deletion or a novel deletion involving PMP22 (in 80%), or a PMP22 sequence variant (in 20%) identified by molecular genetic testing.

Management: Treatment of manifestations: Treatment is symptomatic and involves occupational therapy and physical therapy as needed to address issues with fine motor and gross motor skills, including activities of daily living. Bracing, such as with a wrist splint or ankle-foot orthosis, may be useful transiently or in some instances permanently. Special shoes, including those with good ankle support, may be needed. Neuropathic pain can be treated with analgesic medications. Protective pads at elbows or knees may prevent pressure and trauma to local nerves.

Surveillance: Routine screening neurologic examination focused on muscle atrophy, strength, sensory loss, and neuropathic pain; physical and occupational therapy assessments of gross motor and fine motor skills and activities of daily living; foot examinations for pressure sores or poorly fitting footwear.

Agents/circumstances to avoid: Prolonged sitting with legs crossed; prolonged leaning on elbows; occupations requiring repetitive movements of the wrist; rapid weight loss; vincristine.

Evaluation of relatives at risk: Asymptomatic relatives at risk may wish to clarify their genetic status by undergoing molecular genetic testing for the PMP22 pathogenic variant identified in an affected family member in order to be advised about agents and circumstances to avoid.

Genetic counseling: HNPP is inherited in an autosomal dominant manner. Approximately 20% of individuals with HNPP have the disorder as the result of a de novo PMP22 pathogenic variant. Each child of an affected individual is at a 50% risk of inheriting the PMP22 pathogenic variant. Once the PMP22 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.