Emery-Dreifuss muscular dystrophy (EDMD) is a rare, genetically diverse muscle disorder characterized by a distinct clinical presentation. It is associated with mutations in several genes, many of which encode proteins of the nuclear envelope.

Clinical Features

• Age of Onset: Symptoms typically appear between 2–15 years but can manifest later.
• Muscle Weakness:
  • Slowly progressive humeroperoneal muscle weakness (biceps, triceps, and peroneal muscles).
  • Early signs include ankle and elbow contractures and spinal rigidity.
  • Muscle weakness progresses slowly, with foot drop and eventual non-ambulance in 10% of patients by the third to fifth decades.
• Cardiac Involvement:
  • Severe in those with LMNA mutations.
  • ECG findings include atrioventricular block, small T waves, atrial arrhythmias, and complete heart block.
  • Patients are at risk of atrial fibrillation, atrial paralysis, dilated cardiomyopathy, and ventricular tachyarrhythmias, potentially leading to sudden death.
  • Cardiac involvement does not correlate with the severity of muscle weakness.
• Respiratory Complications:
  • Nocturnal hypoventilation requiring ventilatory support in some patients.

Genetics and Pathophysiology

• X-linked EDMD: Caused by mutations in:
  • EMD (encoding emerin)
  • FHL1 (filamin-1)
• Autosomal Dominant EDMD (AD EDMD): Caused by mutations in:
  • LMNA (lamins A and C)
  • TMEM43 (LUMA)
  • Rarely, SYNE1 (nesprin 1) and SYNE2 (nesprin 2)
• These proteins are involved in maintaining nuclear envelope integrity, crucial for skeletal and cardiac muscle function.

Diagnostic Investigations

• Creatine Kinase (CK): Elevated levels (2–10 times normal).
• Electromyography (EMG): Myopathic changes.
• Muscle Imaging (MRI): Demonstrates selective muscle involvement.
• Muscle Biopsy:
  • Myopathic and dystrophic changes.
  • Type 1 fiber predominance with angular, atrophic fibers.
  • Immunohistochemistry shows absence of emerin staining in most X-linked EDMD cases.
• Genetic Testing: Guided by algorithms due to genetic heterogeneity.

Management

• Supportive Care:
  • Physiotherapy to manage joint contractures.
  • Orthopedic interventions as needed.
• Cardiac Monitoring:
  • Regular Holter monitoring and echocardiography for all patients and at-risk family members.
  • Pacemaker or implantable cardiac defibrillator insertion for junctional bradycardia or atrioventricular block.
  • Cardiac transplantation for severe ventricular failure.
• Respiratory Support:
  • Nocturnal ventilatory support in cases of hypoventilation.

• Genetic Counseling: Recommended for patients and families.

Prognosis

The course of EDMD is variable and influenced by the degree of cardiac involvement, which is often the most critical determinant of outcomes. Early diagnosis and multidisciplinary management can help mitigate complications and improve quality of life.