A dominantly inherited peripheral neuropathy characterized by an abnormal susceptibility to pressure-induced nerve palsies.

Overview

• Definition: A dominantly inherited peripheral neuropathy characterized by an abnormal susceptibility to pressure-induced nerve palsies.
• Epidemiology: Rare in childhood; more common in adolescence and adulthood.
• Pathophysiology:
  • Caused by a deletion on chromosome 17 affecting the PMP22 gene, the same region duplicated in Charcot-Marie-Tooth disease type 1A (CMT1A).
  • Unequal crossing-over during meiosis is the proposed mechanism.
  • Some cases linked to point mutations in PMP22 gene without a deletion.

Clinical Features

• Onset:
  • Symptoms may appear in childhood (first decade), but later onset is more typical.
• Common presentations:
  • Mononeuropathies affecting individual nerve trunks.
    • Common peroneal nerve: Weakness after squatting or sitting cross-legged.
    • Ulnar nerve: Symptoms after elbow pressure.
    • Radial nerve: Affected in the spiral groove.
    • Median nerve: Involvement at the wrist (carpal tunnel syndrome).
  • Brachial plexus neuropathy: Seen less frequently.
• Triggering events:
  • Prolonged pressure, specific postures, or mild trauma.
  • Brief intense physical efforts or sports.
• Recovery:
  • Often complete within days to weeks.
  • Rarely progresses to generalized motor and sensory neuropathy.

Electrophysiological and Imaging Features

• Electrophysiology:
  • Generalized slowing of nerve conduction velocities.
  • Prolonged distal motor and sensory latencies.
  • Findings may be evident in asymptomatic relatives.
• Imaging:
  • MRI may reveal lesions resembling those seen in multiple sclerosis in rare cases.
• Nerve biopsy:
  • Not routinely performed.
  • Shows tomacula (focal thickening of myelin sheaths) in select cases.

Diagnosis

• Clinical suspicion:
  • Disproportionate response to minor trauma or pressure.
  • History of similar symptoms in family members.
• Electrophysiology:
  • Confirms underlying neuropathy.
  • Detects slowed conduction velocities beyond the affected region.
• Genetic testing:
  • Identifies PMP22 deletion or point mutations.
• Differential diagnosis:
  • Multifocal neuropathy without pressure sensitivity.
  • Other hereditary neuropathies (e.g., CMT1A).
  • Acquired neuropathies.

Management

• Lifestyle modifications:
  • Avoidance of pressure-inducing activities and repetitive trauma.
  • Ergonomic adjustments to daily routines.
• Physical therapy:
  • To prevent complications and optimize recovery.
• Prognosis:
  • Recovery is often good, but repeated episodes may lead to residual deficits.
• Monitoring:
  • Surveillance of affected individuals and at-risk family members.
  • Early identification of neuropathic changes to prevent further damage.

Key Points

• HNPP is a genetic neuropathy with specific triggers and a distinct electrophysiological profile.
• Genetic testing and family history are pivotal for diagnosis.
• Lifestyle adjustments and supportive care form the cornerstone of management.
• The absence of curative treatment necessitates prevention-focused strategies.