A 5-year-old boy, Charlie, comes to see you with his parents. His parents and teachers are concerned that he struggles to keep up with his peers in physical exercise. They have also noticed that he is quite clumsy, struggles to climb stairs and gets tired easily. On examination you note that he has a ‘waddling gait’, calf hypertrophy and turns prone and climbs up his legs with his hands to stand from a supine position (Gower’s sign).
From the history and examination, you are concerned that Charlie might have Duchenne’s Muscular Dystrophy (DMD) and decide to perform some investigations.
What is DMD?
DMD is a severe, progressive, muscle wasting disease. It is the most common type of muscular dystrophy. In the UK, around 100 boys are born with DMD each year and there are approximately 2500 people, in the UK, living with it at any one time. DMD is an X-linked recessive inherited disorder, therefore it predominantly affects boys (girls are affected in very rare circumstances).
DMD is due to a mutation in the gene that encodes for the protein dystrophin. This is found on the short arm of the X chromosome (locus Xp21) and leads to an absence of this protein. Dystrophin is an important structural component of skeletal and cardiac muscle. In its absence, there is weakening of the sarcolemma and excess calcium ions can penetrate the muscle membrane, altering signalling and leading to free radical damage. This ultimately leads to progressive muscle degeneration and necrosis, seen as progressive muscular weakness and atrophy.
How is DMD inherited?
In two-thirds of cases, DMD is inherited as an X-linked recessive disorder from a mother who carries a mutation on the X chromosome at locus Xp21, however one-third are due to de novo mutations.
A mother who is a carrier of an X-linked recessive disorder will have a 25% chance of having an affected son and a 25% chance of having a carrier daughter. A father who is affected by an X-linked recessive disorder will have no affected sons, but all of his daughters will be carriers. With de novo mutations, the risk of having a further affected child is lower.
What are the signs and symptoms of DMD?
Symptoms of DMD usually start to develop between 1-3 years of age. However, diagnosis is often delayed with symptoms being explained as part of the normal spectrum of development, for example turning prone to stand can be normal until the age of 3. The average age for diagnosis is 5.5 years.
Presenting signs and symptoms include:
- Delayed motor milestones
- Delayed ability to sit, stand or walk
- Difficulty/Inability to run, hop or jump
- Difficulty climbing stairs or climbing stairs one at a time
- Abnormal gait – due to weaker hip and knee extensors than flexors
- Waddling gait
- Toe walking
- Exaggerated lumbar lordosis
- Gower’s sign
- Hypertrophy of the calf muscles
- Recurrent falls or clumsiness
- Failure to thrive
- Global developmental delay
- Speech delay
- Learning difficulties
How to diagnose DMD?
The most important initial investigation when a diagnosis of DMD is suspected is serum creatinine kinase. The CK will be very high, with levels 10-100x the upper limit of normal.
It is essential that blood is then sent for genetic testing to identify the specific DMD mutation.
Muscle biopsy can be used to confirm the diagnosis of DMD, particularly where genetic testing fails to identify a specific causal mutation. In DMD, on staining of the muscle specimen, there will be a complete absence of dystrophin.
Always consider DMD in boys not walking by 18 months, with delayed motor milestones or global developmental delay
Perform a CK if suspicious of DMD
Remember that a diagnosis of DMD can be devastating, affecting the entire family unit, ensure psychosocial support is offered early on
Management is complex involving the whole multidisciplinary team; aiming to help the child reach their goals, preserve muscle strength and prevent cardiorespiratory complications, as far as possible.
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NHS UK. Muscular dystrophy. Crown copyright 2021.
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Van Ruiten HJA, Straub V, Bushby K, et al. Improving recognition of Duchenne muscular dystrophy: a retrospective case note review. Archives of Disease in Childhood 2014. 99 (1074-1077).