Muscular Dystrophy

Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. These disorders vary in terms of which muscles are primarily affected, the extent of weakness, the rate of progression, and the age of onset. Some types also involve other organ systems.

In affected muscle (right), the tissue has become disorganised and the concentration of dystrophin (green) is greatly reduced, compared to normal muscle (left).

Signs and Symptoms

Severe limb deformities and contractures indicative of muscular dystrophy

The signs and symptoms of muscular dystrophy include progressive muscular wasting, poor balance, scoliosis (curvature of the spine), progressive inability to walk, waddling gait, calf deformation, limited range of movement, respiratory difficulty, cardiomyopathy, muscle spasms, and Gowers' sign.

Causes

Muscular dystrophies are primarily inherited and can follow X-linked recessive, autosomal recessive, or autosomal dominant patterns. In some cases, the disorder arises from spontaneous (de novo) mutations. These genetic mutations usually affect the production of muscle proteins, such as dystrophin, which is essential for muscle fibre strength and protection.

Diagnosis

Diagnosis often involves a combination of muscle biopsy, increased creatine phosphokinase (CpK3) levels, electromyography, and genetic testing. A physical examination and detailed medical history are also important. Specific muscle groups are affected by different types of muscular dystrophy. MRI can be used to assess white matter in the nervous system and measure merosin levels, especially in young boys.

Classification

Duchenne Muscular Dystrophy (DMD)

• OMIM: 310200
• Gene: DMD
• Inheritance Pattern: X-linked recessive
• Age of Onset: Childhood
• Muscles Affected: Distal limbs progressing to generalised weakness, involving respiratory muscles

Becker Muscular Dystrophy

• OMIM: 300376
• Gene: DMD
• Inheritance Pattern: X-linked recessive
• Age of Onset: Childhood
• Muscles Affected: Distal limbs progressing to generalised weakness

Congenital Muscular Dystrophy

• OMIM: Multiple
• Gene: Multiple
• Inheritance Pattern: Autosomal dominant, autosomal recessive
• Age of Onset: At birth
• Muscles Affected: Generalised weakness

Facioscapulohumeral Muscular Dystrophy

• OMIM: 158900
• Gene: DUX4
• Inheritance Pattern: Autosomal dominant
• Age of Onset: Adolescence
• Muscles Affected: Face, shoulders, upper arms, progressing to other muscles

Limb–Girdle Muscular Dystrophy

• OMIM: Multiple
• Gene: Multiple
• Inheritance Pattern: Autosomal dominant, autosomal recessive
• Age of Onset: Any
• Muscles Affected: Upper arms and legs

Myotonic Muscular Dystrophy

• OMIM: 160900, 602668
• Gene: DMPK, CNBP
• Inheritance Pattern: Autosomal dominant
• Age of Onset: Adulthood
• Muscles Affected: Skeletal muscles, heart, other muscle groups

Treatment

There is no cure for muscular dystrophy. Various treatments can help manage symptoms and improve quality of life. These include pharmacotherapy with drugs such as glucocorticoids (e.g., Deflazacort), calcium channel blockers (e.g., Diltiazem), anticonvulsants, and histone deacetylase inhibitors (e.g., Givinostat). Physical therapy, occupational therapy, and orthotic interventions (e.g., ankle-foot orthosis) can assist with mobility and daily activities. Assisted ventilation may be necessary for those with respiratory muscle weakness.

Ankle foot orthosis

Low-intensity, assisted exercises and dynamic exercise training can help delay functional loss. Occupational therapy can enhance the ability to perform daily activities and address environmental modifications to support independence.

Prognosis

Prognosis varies depending on the type of muscular dystrophy. Some types cause severe physical disability and may shorten life expectancy due to respiratory or cardiac complications. Other types may result in relatively mild impairment without significantly affecting lifespan.

History

In the 1860s, boys with progressive weakness and early death were increasingly documented in medical literature. French neurologist Guillaume Duchenne provided a comprehensive account of the most severe form, now known as Duchenne muscular dystrophy.

Society and Culture

In 1966, Jerry Lewis and the Muscular Dystrophy Association (MDA) initiated The Jerry Lewis Telethon, raising awareness and funds for muscular dystrophy. However, the telethon has been criticised for portraying those with the disease as objects of pity. The MD CARE Act, signed into law in 2001 in the US, supports research and established the Muscular Dystrophy Coordinating Committee to focus research efforts.

Self-assessment MCQs (single best answer)

What is the primary cause of muscular dystrophy?

score 0 / 1. running total: 0 / 0

Which protein is notably reduced in concentration in affected muscle tissues in muscular dystrophy?

score 0 / 1. running total: 0 / 0

What is the inheritance pattern of Duchenne Muscular Dystrophy (DMD)?

score 0 / 1. running total: 0 / 0

Which type of muscular dystrophy typically presents at birth?

score 0 / 1. running total: 0 / 0

Which diagnostic method involves sampling and analysing muscle tissue?

score 0 / 1. running total: 0 / 0

What is the common symptom of myotonic muscular dystrophy?

score 0 / 1. running total: 0 / 0

What is one of the therapeutic interventions for managing symptoms of muscular dystrophy?

score 0 / 1. running total: 0 / 0

Which gene is associated with Facioscapulohumeral Muscular Dystrophy?

score 0 / 1. running total: 0 / 0

What is Gowers' sign indicative of?

score 0 / 1. running total: 0 / 0

When was the Muscular Dystrophy Coordinating Committee established in the US?

score 0 / 1. running total: 0 / 0