Overview

• Definition: A dominantly inherited condition characterized by recurrent episodes of brachial plexopathy with pain and weakness.
• Epidemiology:
  • Onset typically in the second decade.
  • Early onset can occur, including congenital brachial plexus palsy at birth.
• Genetics:
  • SEPT9 (Septin 9) gene mutations in ~50% of families.
  • Specific mutation: Arg88Trp associated with characteristic dysmorphic features.

Clinical Features

• Pain:
  • Intense, often the first symptom.
  • Precedes weakness by a few days.
• Weakness:
  • Typically proximal, affecting muscles innervated by the brachial plexus.
  • Persists for variable periods.
  • Recovery is usually complete within weeks to months.
• Pattern of involvement:
  • Brachial plexus: Most commonly affected.
  • May involve single branches (e.g., long thoracic nerve, leading to isolated serratus anterior palsy).
  • Rarely involves phrenic nerve or causes lumbar plexopathy.
• Dysmorphic features (in some families):
  • Craniofacial features: Closely spaced eyes, short palpebral fissures, epicanthus.
  • Other features: Short stature, partial syndactyly, cleft uvula or palate.
• Recurrence:
  • Highly variable frequency among individuals and families.

Pathophysiology

• Genetic Basis:
  • Mutations in SEPT9, often linked with dysmorphism.
  • Inheritance is autosomal dominant.
• Histopathology:
  • Nerve biopsies may show:
    • Inflammatory infiltrates.
    • Acute axonal degeneration.

Diagnosis

• Clinical suspicion:
  • History of recurrent, episodic brachial plexopathy with characteristic pain and proximal weakness.
  • Family history of similar episodes or congenital presentations.
• Genetic testing:
  • Confirms mutations in the SEPT9 gene.
• Differential diagnosis:
  • Non-hereditary neuralgic amyotrophy.
  • Other hereditary neuropathies (e.g., HNPP).
  • Inflammatory or traumatic plexopathies.

Management

• Acute episodes:
  • Pain management:
    • Prednisolone may shorten pain duration and improve symptoms.
    • Other symptomatic treatments as needed.
  • Supportive care:
    • Physical therapy to prevent contractures and optimize recovery.
• Long-term care:
  • Monitoring for recurrence and complications.
  • Genetic counseling for affected families.
• Prognosis:
  • Recovery is typically good but may take weeks to months.
  • Recurrent episodes may lead to cumulative weakness in rare cases.

Key Takeaways

• Hereditary neuralgic amyotrophy is a genetic brachial plexopathy with episodic pain and weakness.
• Genetic mutations in SEPT9 are diagnostic in many cases, with associated dysmorphic features providing additional clues.
• Management focuses on symptom control and preventing complications, with good recovery in most cases.