Duchenne Muscular Dystrophy

Pronunciation: /duːˈʃɛn/
Specialties: Paediatric neurology, neuromuscular medicine, medical genetics

Signs and Symptoms

Duchenne muscular dystrophy (DMD) is characterised by progressive muscle weakness due to muscle fibre degradation and replacement with connective tissue or fat. Initial symptoms commonly appear before age five, often noticed when a child takes their first steps. The disease primarily affects the voluntary muscles, starting with the hips, pelvic area, thighs, and calves, and eventually progressing to the shoulders, neck, and arms.

Key signs include difficulty with motor skills, frequent falls, and walking on toes due to shortening of the Achilles tendon. By around age 13, most affected individuals lose the ability to walk. Cardiomyopathy, particularly dilated cardiomyopathy, is common, and respiratory impairment can occur in later stages. Gowers's sign, where a child uses their hands to "walk" up their legs to stand, is classic for DMD.

Cause

DMD is caused by mutations in the dystrophin gene located on the X chromosome, leading to a significant reduction or absence of dystrophin protein. This protein is very important for maintaining muscle cell membrane integrity. DMD follows an X-linked recessive inheritance pattern, primarily affecting males.

Diagnosis

Diagnosis is often confirmed via genetic testing, which can identify mutations in the dystrophin gene. Elevated creatine kinase levels in the blood also indicate muscle damage. If genetic testing is inconclusive, a muscle biopsy can be performed to check for the presence of dystrophin.

DNA Test

DNA testing can identify the specific exon mutations in the dystrophin gene, confirming the diagnosis in most cases.

Muscle Biopsy

When DNA testing fails, a muscle biopsy may be performed. Tests like immunohistochemistry and immunoblotting for dystrophin provide information on the presence or absence of the protein.

Prenatal Tests

Prenatal testing is available for known carriers. Techniques include chorion villus sampling (CVS) and amniocentesis, though these carry a small risk of miscarriage.

Treatment

There is no cure for DMD, and treatment focuses on symptom management to maximise quality of life. Treatments include:

• Corticosteroids such as prednisolone and deflazacort, which can improve muscle strength and prolong walking ability.
• Physical Therapy to maintain muscle strength and flexibility, and to minimise contractures.
• Orthopaedic Appliances like braces and wheelchairs to improve mobility.
• Respiratory Support as the disease progresses.
• Cardiac Care which may include pacemakers for cardiac issues.

Medications like eteplirsen, ataluren, golodirsen, viltolarsen, and casimersen target specific genetic mutations and have shown varying levels of efficacy. Comprehensive care guidelines have been developed by the US Centres for Disease Control and Prevention.

Prognosis

DMD is a progressive disease that affects all voluntary muscles, eventually involving the heart and respiratory muscles. The median life expectancy is around 28–30 years, though some individuals may live into their 30s or 40s with excellent medical care. Respiratory failure and cardiac complications are the most common causes of death.

Epidemiology

DMD is the most common type of muscular dystrophy, affecting about one in 5,000 males at birth. It has an incidence of one in 3,600 male infants. The prevalence is higher among Hispanic populations compared to non-Hispanic Whites and non-Hispanic Blacks.

History

DMD was first described by Giovanni Semmola in 1834 and Gaetano Conte in 1836. The French neurologist Guillaume Duchenne de Boulogne provided a detailed account in 1861, from whom the disease gets its name. Duchenne was also the first to perform a muscle biopsy for microscopic examination.

Research

Efforts are ongoing to find treatments that restore dystrophin production or block calcium ion entry into muscle cells. Techniques like exon-skipping and gene therapy using CRISPR/Cas9 are being looked at, along with medications to address the root cause of the disease.

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Self-assessment MCQs (single best answer)

What is the primary cause of Duchenne muscular dystrophy (DMD)?

At what age do initial symptoms of DMD commonly appear?

Which of the following muscles are affected first in DMD?

Which sign is classic for DMD, where a child uses their hands to "walk" up their legs to stand?

What type of inheritance pattern does DMD follow?

Which diagnostic method is often used to confirm DMD by identifying mutations in the dystrophin gene?

What is the function of the dystrophin protein affected in DMD?

What is the median life expectancy for individuals with DMD?

Which treatment option is NOT typically used to manage symptoms of DMD?

Who provided the detailed account of DMD in 1861, from whom the disease gets its name?