Makindo Medical Notes

Related Subjects: |Autosomal Dominant |Autosomal Recessive |X Linked Recessive

About

• Limb Girdle Muscular Dystrophy (LGMD): A group of genetically heterogeneous disorders characterized by progressive weakness of the pelvic and shoulder girdles.
• Both autosomal dominant (LGMD1) and autosomal recessive (LGMD2) inheritance patterns are seen.

Aetiology

• Caused by mutations in various genes encoding proteins involved in muscle function and structure, including:
  • Dystrophin: Mutations linked to muscle fiber membrane stability.
  • Sarcoglycan: Involved in the sarcoglycan complex, maintaining the integrity of muscle cell membranes.
  • Dysferlin: Plays a role in muscle membrane repair.
  • Mutations in other genes such as Calpain, Telethonin, and Caveolin have also been implicated.

Clinical Features

• Progressive muscle weakness: Weakness predominantly affects the muscles of the shoulder and pelvic girdles.
• Cardiomyopathy: Some forms of LGMD are associated with heart muscle involvement, leading to dilated cardiomyopathy.
• Respiratory muscle involvement: Advanced cases may lead to respiratory insufficiency, requiring ventilatory support.
• Clinically, LGMD presents similarly to Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD), but with later onset and slower progression in some cases.

Investigations

• Creatine Kinase (CK) levels: Typically elevated, reflecting ongoing muscle damage.
• Electromyography (EMG): Confirms a primary myopathic process, showing characteristic myopathic changes.
• Genetic analysis: Essential for identifying specific gene mutations and determining the inheritance pattern.
• Cardiac assessment: Echocardiogram (ECHO) and Electrocardiogram (ECG) are important for detecting cardiomyopathy, which is common in certain subtypes of LGMD.

Management

• Multidisciplinary approach: Involves neurologists, cardiologists, pulmonologists, physiotherapists, and genetic counselors to manage the diverse manifestations of the disease.
• Cardiac management: Regular cardiac monitoring and management of cardiomyopathy with medications such as ACE inhibitors or beta-blockers.
• Respiratory support: Non-invasive ventilation may be needed in advanced cases with respiratory muscle involvement.
• Physiotherapy: Regular physical therapy can help maintain muscle strength and function, preventing contractures and improving mobility.
• Genetic counseling: Essential for patients and families to understand the inheritance pattern and implications for future offspring.
• Prognosis: Highly variable depending on the specific genetic mutation and subtype of LGMD. Some patients have a slow progression, while others may develop significant disability.

Cases — Limb-Girdle Muscular Dystrophy (LGMD)

• Case 1 — Adolescent with Proximal Weakness 👣: A 15-year-old boy develops difficulty climbing stairs and rising from the floor. Exam: proximal weakness of pelvic and shoulder girdle, preserved facial and ocular muscles. No calf pseudohypertrophy. CK markedly elevated. Diagnosis: Limb-girdle muscular dystrophy (autosomal recessive, likely sarcoglycanopathy). Management: Supportive — physiotherapy, orthotics, genetic counselling, cardiac monitoring.
• Case 2 — Adult-Onset Slowly Progressive Weakness ⏳: A 30-year-old woman reports progressive difficulty lifting her arms overhead and rising from a chair over 5 years. Family history: cousin with similar symptoms. Exam: symmetric shoulder and hip girdle weakness, waddling gait, no cognitive impairment. Diagnosis: Autosomal dominant LGMD (e.g., LGMD1). Management: Physiotherapy, genetic testing, monitoring for cardiomyopathy and respiratory weakness.
• Case 3 — LGMD with Cardiac Involvement ❤️: A 22-year-old man with known LGMD presents with palpitations and dyspnoea. ECG: conduction abnormalities; echo: dilated cardiomyopathy. Exam: proximal limb weakness, Gower’s sign positive. Diagnosis: LGMD with cardiac involvement (e.g., lamin A/C mutation). Management: Cardiology follow-up (possible pacemaker/ICD), respiratory support, MDT input for mobility and daily living aids.

Teaching Commentary 🧠

Limb-Girdle Muscular Dystrophies are a genetically diverse group of disorders causing progressive proximal weakness, sparing the face and ocular muscles (unlike FSHD or myotonic dystrophy). - Onset: childhood to adulthood. - Inheritance: autosomal recessive more common, but dominant forms exist. - Features: waddling gait, Gower’s sign, proximal limb wasting; CK elevated; some subtypes involve cardiac and respiratory complications. Dx: genetic testing, muscle biopsy (dystrophic pattern). Mx: supportive — physio, OT, respiratory and cardiac surveillance, genetic counselling. Prognosis varies widely depending on subtype.