Clinical Guidance

More than 26 single PMP22 nucleotide variants have been reported to cause HNPP. It is not clear if there are genotype-phenotype correlations with these variants since each is limited to a few families . Of note, six families with the PMP22 frameshift variant have a typical HNPP phenotype and are also more likely to have an associated clinically evident motor/sensory neuropathy mimicking Charcot-Marie-Tooth neuropathy type 1 (CMT1; see CMT Overview) . A similar phenotype has been described in individuals with other single-nucleotide variants in PMP22 [, , , , ].

Source: GeneReviews — "Hereditary Neuropathy with Liability to Pressure Palsies"

Penetrance

Penetrance is 100% but expressivity is highly variable even within the same family. For an unknown reason men typically have more severe clinical nerve palsies and electrophysiologic studies.

Source: GeneReviews — "Hereditary Neuropathy with Liability to Pressure Palsies"

Diagnostic Criteria

Suggestive Findings

Hereditary neuropathy with liability to pressure palsies (HNPP) should be suspected in individuals with the following clinical findings, electrophysiologic studies, imaging studies, and family history.

Typical clinical findings

• Recurrent acute focal sensory and motor neuropathies mainly at entrapment sites

• Painless nerve palsy after minor trauma or compression

• Evidence on physical examination of previous nerve palsy such as focal weakness, atrophy, or sensory loss

• Complete spontaneous recovery from neuropathies (in 50% of occurrences) within weeks

• Mild-to-moderate pes cavus foot deformity (in 4%-40% of individuals)

Electrophysiologic studies

Source: GeneReviews — "Hereditary Neuropathy with Liability to Pressure Palsies"

Differential Diagnosis

The signs and symptoms of compression neuropathy in hereditary neuropathy with liability to pressure palsies (HNPP) are the same as those of the acquired type. Thus, HNPP is part of the broad differential diagnosis of both compression neuropathies and general peripheral neuropathies, including the hereditary neuropathies and Charcot-Marie-Tooth (CMT) syndrome (see CMT Overview).

Acquired Disorders

Compression neuropathies. Pressure palsies are most commonly the result of environmentally acquired physical compression of peripheral nerves. The most common are carpal tunnel syndrome with compression of the median nerve at the wrist,* peroneal pressure palsy with compression of the superficial peroneal nerve at the fibular head, and ulnar nerve compression at the elbow.

Source: GeneReviews — "Hereditary Neuropathy with Liability to Pressure Palsies"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with hereditary neuropathy with liability to pressure palsies (HNPP), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 2.

Recommended Evaluations Following Initial Diagnosis in Individuals with HNPP

System/Concern | Evaluation | Comment

Neurologic

| Neurologic eval | To evaluate for pain determine:

• Extent of weakness atrophy, pes cavus, gait stability, sensory loss

• If there are assoc manifestations (e.g., focal atrophy or sensory loss in less common sites of entrapment)

• If affected person /or a family member has had episodes of acute transient nerve palsy

Musculoskeletal

| Orthopedics/ physical medicine rehab/ PT/OT evaluation | To incl assessment of:

• Gross motor fine motor skills need for PT (to improve gross motor skills) /or OT (to improve fine motor skills)

• Feet for evidence of pes cavus need for AFOs, specialized shoes

• Mobility, ADL, need for adaptive devices

• Need for handicapped parking

Genetic

counseling | By genetics professionals1 | To inform affected persons families re nature, MOI, implications of HNPP to facilitate medical personal decision making

Family support

resources | Assess need for:

• Community resources (e.g., Parent to Parent);

• Social work involvement for parental support.

Source: GeneReviews — "Hereditary Neuropathy with Liability to Pressure Palsies"

Clinical Guidance

Activities that are risk factors for pressure palsies include the following :

• Prolonged sitting with legs crossed

• Prolonged leaning on elbows

• Occupations requiring repetitive movements of the wrist

• Rapid weight loss

• Wearing a heavy backpack on shoulders

Particular care must be taken in positioning during surgery (particularly knee surgery) to avoid nerve compression . Vincristine, commonly used in the chemotherapy of lymphoma, has been reported to exacerbate HNPP, as other potential neurotoxic chemotherapy or agents . Medications that are toxic or potentially toxic to persons with CMT comprise a spectrum of risk ranging from definite high risk to negligible risk. See the Charcot-Marie-Tooth Association website (pdf) for an up-to-date list.

Source: GeneReviews — "Hereditary Neuropathy with Liability to Pressure Palsies"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Hereditary Neuropathy with Liability to Pressure Palsies"

Surveillance Guidelines

Table 3.

Recommended Surveillance for Individuals with HNPP

System/Concern | Evaluation | Frequency

Neurologic

| Screening neurologic exam focused on muscle atrophy, strength, sensory loss | Annually

Eval for neuropathic pain

Musculoskeletal

| PT (gross motor skills) ADL

OT (fine motor skills) ADL

Foot examination

| For pressure sores or poorly fitting footwear | Annually by physician; at more frequent intervals by affected person

ADL = activities of daily living; OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "Hereditary Neuropathy with Liability to Pressure Palsies"