Raju is a 4 year old boy who presents to his local doctor after teachers have commented that he seems to fall over a lot in the play ground and doesn’t run as fast as his friends. Mum is not overly concerned although she has noticed that his stamina is not great as he often asks to be carried when they are out shopping. But she just thought he might be a bit lazy. He never complains of any pain in his legs. He has not lost any weight recently and generally is very well.
Raju was born full term, his birth weight was 3.4kg. He is the first child in the family. Both mum and dad are well and they are not aware of any significant illnesses running in the family.
Raju was well at birth and mum described him as a thriving and chubby baby who breast fed well. He rolled at 6 months and pulled up to stand at 14 months. He cruised at 16 months and walked at 20 months. He started talking in short sentences at the age of 3 and is currently awaiting a speech and language assessment as pre-school.
The local doctor observes Raju walking into the consultation room and he notices a broad based gait. Raju is walking well but seems unsteady on his legs when picking up a toy from the floor. He seems to push himself up on his legs to get himself up. His height and weight are both on the 50th centile.
On inspection, Raju has strong legs with large calf muscles. There is no muscle wasting. His skin looks unremarkable with no bruising and no rash.
Examination of if his musculoskeletal system seems unremarkable (pGALS). His joint examination is normal; there is no swelling, redness or increased temperature in any of his joints. He has a normal range of movements in both his arms and legs. There is no stiffness in any of the joints.
Further examination does not reveal any abnormalities. His respiratory, cardiovascular and abdominal examination are unremarkable. The local doctor attempts a neurological examination but Raju is uncooperative. The local doctor does not detect any obvious abnormalities in reflexes, tone and power.
What are the red flags in this history?
- Slightly delayed motor development (see section on motor milestones)
- Frequent falls
- Seems to struggle to get up from the floor, using hands to “walk up legs” (Gower sign)
- Mild speech delay.
What are the red flags on observation/examination?
- Broad based gait in a child > age 2. This is abnormal and may indicate muscle weakness
- Enlarged calves (calf hypertrophy); this is typically seen in Duchenne muscular dystrophy. It is pseudohypertrophy as it is due to fat and connective tissue that have replaced the damaged muscle cells.
- There may be hypotonia but this can be difficult to detect in young children.
What is the likely diagnosis?
The combination of waddling gait, frequent falls, mildly delayed motor development and mild speech delay point to a muscle disorder (myopathy). There are many different types but the most common is Duchenne muscular dystrophy.
Which blood test should the GP request?
Creatine phosphokinase (CPK); this test is a highly useful test for muscular dystrophies (often elevated 10-100x), and it is elevated from birth. If CPK is normal then muscular dystrophy can be excluded as a diagnosis. The local doctor also orders a complete blood count (CBC), electrolytes, liver profile (LFTs) and bone profile.
These are the results:
Normal complete blood count
Urea and electrolytes normal
LFTs, (liver function tests) ALT (alanine transferase) 341 (12-60)
CPK is often extremely elevated in muscular dystrophies. ALT can also be raised; this is not a sign of liver failure but this further indicates muscle breakdown (ALT is produced by damaged muscle and/or liver cells). The local doctor tells the mother that there seems to be a problem with Raju's muscles and she refers Raju urgently to the paediatric team with expertise in neuromuscular diseases.
What other test is needed?
Blood test for DNA analysis (looking for a mutation in the dystrophin gene)
The most likely diagnosis is Duchenne muscular dystrophy. The combination of the red flags in the clinical history and the elevated CPK is highly suggestive. DNA testing for mutation in the dystrophin gene will give the diagnosis in most cases.
What is the inheritance patterns of this condition?
The DMD gene is located on the X chromosome. Boys have one X chromosome and one Y chromosome, girls have two X chromosomes. Women carry the DMD gene but this does not usually cause muscle problems. This is because women have two X chromosomes and the unaffected X chromosome can compensate for the faulty one. In contrast boys only have one X chromosome, therefore cannot compensate for the faulty gene. Boys with the faulty gene will therefore always have symptoms of the condition.
In about 70% of the cases the condition is passed on from mother to child (in 30% of the cases, there is a new mutation). For a mother carrying the DMD gene, there is a 50% chance she passes on her faulty X chromosome on to her child. That means that if the child is a boy, he has a 50% chance to be affected by Duchenne muscular dystrophy. If it is a girl, she has a 50% chance of being a carrier of Duchenne muscular dystrophy. This is called X-linked inheritance and typically affects single genes.
What treatment is the current standard in this condition?
The current standards of care (see The Diagnosis and Management of Duchenne Muscular Dystrophy * ) recommend starting corticosteroids in all boys with Duchenne muscular dystrophy. Corticosteroids are currently the only medication available that slow the decline in muscle strength (keep the boys walking for longer) and this in turn stabilizes respiratory function. There is also limited evidence that corticosteroids protect cardiac function. Steroids are usually started between the ages of 4-8, once muscle function has reached a plateau phase, meaning that the child has reached a “steady state” in muscle function. No new skills are acquired anymore, but before the child’s motor skills start to decline (if frequent falls, reduction in walking distance).
Examples of videos to demonstrate Gower's sign, waddling gait and more information on muscle disease are available.