Duchenne and Becker muscular dystrophy: Viva

Branch 1: Confirming the diagnosis

The candidate should recognise the classic picture of Duchenne muscular dystrophy, with the delayed walking, the frequent falls, the calf pseudohypertrophy, the Gowers sign, the reduced reflexes, and a creatine kinase of 24,000 units per litre that is off the scale. A strong candidate states that the creatine kinase is typically above 10,000 and between 10,000 and 100,000 in Duchenne, that it is raised from birth before any weakness, and that a value of this magnitude in a weak boy points to a dystrophic process until the genetics prove otherwise. The candidate should add that the mildly raised transaminases are muscle-derived, because the same enzymes leak from the damaged fibre, and that a high transaminase in a weak boy is muscle, not liver. ^[3]

If the examiner presses on the confirmation, the candidate should state that the genetic test has now replaced the muscle biopsy as the first investigation, with multiplex ligation-dependent probe amplification as the first-line method for the exon deletions and duplications, and whole-gene sequencing for the point and splice mutations when the multiplex is normal. A muscle biopsy with dystrophin immunostaining is reserved for the inconclusive case. The candidate should offer the carrier testing of the mother and the female relatives, because the disease is X-linked recessive, with about two thirds inherited and one third new mutations. ^[4]