Hereditary neuropathy with liability to pressure palsies

Hereditary neuropathy with liability to pressure palsies (HNPP), also known as tomaculous neuropathy or hereditary pressure-sensitive neuropathy, is a genetic disorder affecting the peripheral nervous system. It is caused by a deletion or, less commonly, a point mutation in the PMP22 gene on chromosome 17p11.2, which encodes peripheral myelin protein 22. This protein is essential for the formation and maintenance of myelin, the insulating sheath that surrounds peripheral nerves. The loss of one functional copy of PMP22 leads to abnormally formed myelin, making nerves unusually susceptible to damage from mechanical stress such as compression, stretching, or repetitive movements. Patients with HNPP typically experience recurrent episodes of numbness, tingling, muscle weakness, and sometimes pain in areas where peripheral nerves are vulnerable to compression — such as the wrists (carpal tunnel), elbows (ulnar nerve), and knees (peroneal nerve). These episodes, often called pressure palsies, are usually triggered by activities that would not cause problems in unaffected individuals, such as leaning on the elbows, crossing the legs, or carrying heavy bags. Episodes may last days to months and often resolve partially or completely, though over time some patients develop a mild chronic peripheral neuropathy with persistent weakness or sensory loss. Nerve conduction studies typically show diffusely slowed conduction velocities and focal conduction abnormalities at common entrapment sites. Nerve biopsy characteristically reveals focal thickenings of the myelin sheath called tomacula. There is currently no cure or disease-modifying treatment for HNPP. Management focuses on prevention and supportive care. Patients are advised to avoid prolonged pressure on nerves, repetitive movements, and sustained postures that compress vulnerable nerve sites. Protective padding (e.g., elbow or wrist pads) and ergonomic modifications may help reduce episodes. Physical and occupational therapy can assist with rehabilitation after episodes. In some cases, surgical decompression of entrapped nerves may be considered, though outcomes can be variable. Genetic counseling is recommended for affected individuals and their families.

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