Hereditary neuropathy with liability to pressure palsies (HNPP) is a demyelinating neurological disorder clinically characterized by recurrent, focal compressions of a peripheral nerve.5 Carpal tunnel syndrome, in which there is similar nerve compression, may be a manifestation of HNPP.5 Also known as tomaculous neuropathy and familial recurrent polyneuropathy, HNPP is one of the most commonly inherited motor sensory neuropathies.1
HNPP is an autosomal dominant disorder caused by a 1.5 megabase deletion of the PMP22 gene encoding peripheral myelin protein 22kD located on chromosome 17p11.2.1 The deletion is detected in most affected individuals,9 but the mechanism of how this deletion results in the symptoms of HNPP is still unclear.1 Some individuals with the HNPP phenotype do not harbor the deletion, but rather a frameshift mutation in the PMP22 gene.5 Also, individuals with HNPP may have a de novo, or sproadic, mutation of the PMP22 gene.5
Symptoms of HNPP usually begin in adolescence or young adulthood.5 Individuals with HNPP clinically present with progressive muscular weakness, numbness, and atrophy.2 Episodic, nonsymmetrical palsies often arise as a result of trauma or compression of the affected nerve.2 HNPP most commonly presents as a mononeuropathy, affecting only one nerve, with an acute onset of a non-painful, focal sensory and motor neuropathy.5 "Multifocal neuropathies, especially entrapment neuropathies, such as carpal tunnel syndrome, may be manifestations of HNPP."2
Electromyography (EMG) of individuals with HNPP typically will show conduction block at the site of nerve entrapment.6 Because these individuals have a demyelinating neuropathy, many may have diffuse and moderate slowing motor and sensory nerve conduction velocities (NCVs) as well as prolonged distal motor and sensory latencies.6 A nerve biopsy typically reveals demyelination and remyelination resulting in "sausage-like" thickening of the myelin sheath, termed "tomacula."2
The focal neuropathy in HNPP is often observed in the peroneal nerve at the fibular head, producing foot drop. Other sites of compression include: the ulnar at the elbow, resulting in hypothenar and interossei muscle weakness and atrophy with sensory loss over the lateral aspect of the hand; and the median nerve at the wrist causing carpal tunnel syndrome with thenar muscle weakness, atrophy, and sensory loss over the thumb and index finger.5 Effects of HNPP may be more mild, for example, weakness in the hands that results in inability to hold or pick up small objects.
The availability of genetic testing for HMSNs assists physicians in clarifying a clinical picture with a molecular diagnosis. For individuals in whom a neuropathy is suspected, but who have a negative family history, a genetic test can indicate the presence of a sporadic mutation in the PMP22 gene.6 "DNA analysis for the deletion of 17p11.2 is clearly useful in establishing the diagnosis of HNPP, which should be considered regardless of family history or clinical evidence of a generalized neuropathy, and in patients with multifocal neuropathies that do not conform to the classic clinical picture of HNPP."6
Obtaining an early diagnosis of HNPP can lead to proper patient management and may help a patient take preventative measures to avoid nerve pressure or trauma to sensitive areas such as the elbow or wrist.2 Because HNPP is usually not severely handicapping, individuals with the disorder can pursue activities of daily living.5 However, various positions, such as prolonged sitting with crossed legs, prolonged leaning on elbows, and repetitive movements of the wrist should be avoided to prevent pressure palsies.5 There is no specific treatment for HNPP, but wrist splint or ankle-foot orthosis may provide relief from foot drop and balance problems.5 Surgical options to alleviate the compression associated with the disorder are still debated:
There is a developing consensus that surgical repair of carpal tunnel syndrome in these [HNPP] patients is of little benefit and transposition of the ulnar nerve at the elbow may actually produce poor results.5
A definitive molecular diagnosis of HNPP may be helpful to:
The following case study of an individual with HNPP demonstrates the usefulness of genetic testing and how it can affect patient management.
Return to HMSN Session
Thank you for participating in NeuroCAST.
