Duchenne and Becker muscular dystrophy: Case

This boy has the classic presentation of Duchenne muscular dystrophy. The delayed walking, the toe-walking gait with lumbar lordosis, the firm calf pseudohypertrophy, the Gowers sign, the proximal weakness worse in the legs, and the reduced reflexes together form a recognisable picture, and the creatine kinase of 31,000 units per litre settles the direction of the workup. The high alanine aminotransferase with a normal bilirubin is muscle-derived, because the same enzymes leak from the damaged fibre, so this is not a liver problem. [3]

Clinical findings and assessment

The key findings are the proximal weakness worse in the legs, the calf pseudohypertrophy, the Gowers sign, the reduced reflexes, and the creatine kinase of 31,000. The weakness is proximal and symmetrical, the pelvic girdle failing before the shoulder girdle, and the face and the eyes are spared, which separates a primary muscle disease from a more generalised neurological process. The firm calves are the pseudohypertrophy of fat and fibrosis that replace the necrotic fibre, and the reduced reflexes reflect the loss of the muscle. The creatine kinase, between 10,000 and 100,000, is off the scale and points to a dystrophic process. [4]

The timed function tests grade and track the disease. The time to stand from the floor, the ten-metre run, the climb of four stairs, and the six-minute walk are measured, because the trend over time reveals the motor plateau that should trigger the glucocorticoid decision and the decline that heralds the loss of ambulation. The joints are checked for the contractures of the Achilles, the hamstrings, and the iliotibial bands, the spine for the scoliosis that will come once he is in a wheelchair, and the heart for the gallop of the early cardiomyopathy. [4]

Diagnostic confirmation

The diagnosis is now confirmed by genetic testing, which has replaced the muscle biopsy as the first investigation. The first-line test is multiplex ligation-dependent probe amplification, which detects the exon deletions and duplications that account for the majority of cases, and if it is normal, whole-gene sequencing finds the point and splice mutations. The reading-frame hypothesis predicts that an out-of-frame deletion produces Duchenne, while an in-frame deletion produces Becker, and the mutation type decides the eligibility for the precision therapies, so the genetic report is read with care. A muscle biopsy with dystrophin immunostaining is reserved for the small number of boys whose genetics are inconclusive. [2][3]

Management

The management rests on a glucocorticoid backbone and a set of systems surveillance, delivered together through a multidisciplinary neuromuscular centre. The glucocorticoid is started at the motor plateau, which this boy has reached, typically between four and seven years. The FOR-DMD trial established prednisolone 0.75 mg per kg per day and deflazacort 0.9 mg per kg per day as equivalent and superior to placebo, with deflazacort producing less weight gain, so either is started now and continued through the loss of ambulation. For this 21 kg boy, prednisolone is about 16 mg per day or deflazacort about 19 mg per day. The bone protection with calcium and vitamin D begins at the same time, and the family is taught the sick-day rule to give stress-dose hydrocortisone for a severe illness or a major operation. [7][4]

The cardiac surveillance begins now, with a baseline echocardiogram and electrocardiogram repeated at least annually, and an angiotensin-converting-enzyme inhibitor started by the age of ten even before symptoms, because the cardiomyopathy is progressive and silent in the young boy. The respiratory surveillance adds spirometry from the age of five or six, and the forced vital capacity is tracked as the bellwether of the decline, with non-invasive ventilation started for the nocturnal hypoventilation when the time comes. The two acute traps are flagged at once, that suxamethonium and volatile anaesthetic agents are contraindicated because of the anaesthesia-induced rhabdomyolysis and hyperkalaemic arrest, and that the glucocorticoid suppresses the adrenal axis so the boy needs stress-dose hydrocortisone when unwell. [5]

The precision therapy

The precision therapy is chosen by the mutation, and the genetic report is read against the drugs. The exon-skipping antisense oligonucleotides restore the reading frame and produce a shorter functional dystrophin, eteplirsen for exon 51 and golodirsen and viltolarsen for exon 53, and ataluren promotes read-through of the nonsense mutation. The adeno-associated-virus gene therapy of delandistrogene moxeparvovec delivers a micro-dystrophin, and it is offered alongside the glucocorticoid backbone rather than instead of it, because the micro-dystrophin is shorter than the native protein and the long-term durability is still being defined. The eligibility is settled by the mutation and the age, in a shared decision with the family. [4]

Outcome and family counselling

The prognosis has been rewritten by the modern care. Untreated, the boy would lose ambulation between nine and eleven years and die of the heart and the lungs in his late teens, but with the glucocorticoid, the cardiac and respiratory surveillance, and the timely ventilation, he is expected to walk into his second decade and survive into his twenties and thirties. The determinants are the completeness and the timing of the care and the mutation that opens a precision-therapy door. [4]

I would counsel the family honestly and warmly. I would explain that their son has Duchenne muscular dystrophy, a genetic condition in which a single missing protein slowly weakens the muscle, that the creatine kinase result confirms the direction, and that the genetic test will settle the exact change and open the door to the precise treatments. I would name the glucocorticoid as the medicine that changes the trajectory, explain its benefits and its side effects in plain words, and teach the sick-day rule and the anaesthetic warning as the two things the family must always remember. I would reassure the family that a team of doctors and therapists will meet their son together, that the heart and the lungs will be watched closely, and that the plan will move with him through his childhood and into his adult life. I would offer the carrier testing of the mother and the female relatives, because the heart of a carrier can fail without warning, and I would return regularly to explain the findings, the plan, and the next steps as the picture becomes clearer. [3]