Muscular Dystrophies

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management | Example Management | References

Definition

Muscular dystrophies (MD) are a group of inherited genetic conditions characterised by progressive muscle weakness and wasting. These disorders primarily affect the muscles used for movement (skeletal muscles), but they can also affect the heart muscles and other organs. The most common types include Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).

Aetiology

Muscular dystrophies are caused by mutations in genes that are involved in maintaining muscle integrity and function. Different types of MD are associated with mutations in different genes:

• Duchenne and Becker muscular dystrophy: Mutations in the dystrophin gene (DMD).
• Myotonic dystrophy: Mutations in the DMPK gene (type 1) or CNBP gene (type 2).
• Limb-girdle muscular dystrophy: Mutations in various genes, including CAPN3, DYSF, and others.
• Facioscapulohumeral muscular dystrophy: Deletion of a genetic material on chromosome 4 (FSHD1) or mutation in the SMCHD1 gene (FSHD2).

Pathophysiology

The mutations in the genes responsible for muscular dystrophy lead to the production of defective proteins that are crucial for muscle fibre integrity and function. In Duchenne and Becker muscular dystrophies, the lack of functional dystrophin protein leads to muscle fibre damage and progressive muscle weakness. The muscle fibres are gradually replaced by fat and connective tissue, leading to the characteristic muscle wasting.

Risk Factors

• Family history of muscular dystrophy.
• Gender: Duchenne and Becker muscular dystrophies predominantly affect males.

Signs and Symptoms

• Progressive muscle weakness and wasting.
• Difficulty walking, frequent falls, and trouble with running or jumping.
• Gowers' sign: Difficulty rising to a standing position.
• Calf hypertrophy (enlarged calf muscles) in Duchenne muscular dystrophy.
• Cardiac issues, including cardiomyopathy and arrhythmias.
• Respiratory difficulties due to weakening of respiratory muscles.
• Myotonia (delayed relaxation of muscles) in myotonic dystrophy.

Investigations

• Clinical history and physical examination, including neurological and muscular assessment.
• Creatine kinase (CK) levels: Elevated CK levels indicate muscle damage.
• Genetic testing to identify specific gene mutations.
• Muscle biopsy to examine the muscle tissue for abnormalities.
• Electromyography (EMG) to assess muscle function.
• Cardiac evaluation, including ECG and echocardiogram, to monitor heart function.

Management

Primary Care Management

• Initial assessment and referral to a neurologist or genetic specialist for further evaluation and diagnosis.
• Supportive care, including managing symptoms and providing information and support to patients and families.
• Coordination of multidisciplinary care, involving physiotherapists, occupational therapists, speech therapists, and dietitians.

Specialist Management

• Corticosteroids (e.g., prednisone, deflazacort) to slow muscle degeneration in Duchenne muscular dystrophy.
• Cardiac medications to manage heart complications.
• Respiratory support, including non-invasive ventilation, for respiratory muscle weakness.
• Physiotherapy to maintain muscle strength and prevent contractures.
• Occupational therapy to assist with daily activities and adaptive equipment.
• Surgical interventions for orthopaedic complications, such as scoliosis.
• Genetic counselling for families.

Example Management for Muscular Dystrophies

A patient presenting with symptoms of muscular dystrophy should be referred to a neurologist for a comprehensive evaluation, including genetic testing and muscle biopsy. If diagnosed with Duchenne muscular dystrophy, corticosteroids may be prescribed to slow muscle degeneration. The patient should receive multidisciplinary care, including physiotherapy to maintain muscle strength, occupational therapy to assist with daily activities, and regular cardiac and respiratory evaluations. Genetic counselling should be offered to the patient and their family. Regular follow-up is necessary to monitor disease progression and adjust the care plan as needed.

References

1. NICE. (2024). Muscular Dystrophy: Assessment and Management. Retrieved from NICE
2. NHS. (2023). Muscular Dystrophy. Retrieved from NHS
3. Moxley, R. T., et al. (2012). Practice Parameter: Corticosteroid Treatment of Duchenne Dystrophy. Neurology.
4. Emery, A. E. H. (2010). The Muscular Dystrophies. The Lancet.
5. McDonald, C. M., et al. (2017). Long-term Pulmonary, Cardiac, and Orthopaedic Outcomes of Duchenne Muscular Dystrophy: A Retrospective Multicentre Study. The Lancet Neurology.

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