Congenital myopathies and muscular dystrophies: SAQ

This boy presents the classic picture of a collagen VI-related congenital muscular dystrophy, most likely Ullrich congenital muscular dystrophy. The proximal joint contractures with the distal joint hyperlaxity and the follicular hyperkeratosis are the hallmark, and the normal brain and the only mildly raised creatine kinase fit the collagen VI spectrum and argue against the merosin-deficient and the dystroglycanopathy forms. The alert infant with the reduced reflexes and the normal brain places the cause in the neuromuscular periphery, and the respiratory involvement is the immediate threat. ^[1]

Question 1 (10 marks)

Outline your diagnostic approach, the investigations you would request, and how you would confirm the diagnosis. ^[1]

My first move is to recognise that this is a neuromuscular cause of the floppy infant, because the baby is socially alert but weak with absent reflexes, which moves the diagnosis from a central to a peripheral cause. The creatine kinase of 420 units per litre is only mildly raised, which forks the diagnosis toward a congenital myopathy or a collagen VI-related muscular dystrophy and away from the merosin-deficient and the dystroglycanopathy forms, in which the kinase runs into the thousands. The proximal contractures with the distal hyperlaxity and the follicular hyperkeratosis are the specific hallmark of the collagen VI spectrum, and the normal brain and the normal eyes fit it. ^[1]

I would request the next-generation sequencing muscle panel, which has replaced the muscle biopsy as the first-line diagnostic test, targeting the collagen VI genes COL6A1 to COL6A3 alongside the other major congenital-muscle-disease genes LAMA2, the dystroglycanopathy genes, LMNA, SEPN1, TTN, RYR1, NEB, and MTM1. I would add the nerve conduction studies, which may show a mild neuropathy in some collagen VI cases, and I would reserve the muscle biopsy with the collagen VI immunohistochemistry for the panel-negative case. I would send the survival motor neuron gene test only if the panel were pending and the picture were ambiguous, to exclude spinal muscular atrophy, which has a specific disease-modifying therapy. ^[1][4]

I would complete the baseline with the echocardiogram and the electrocardiogram to screen the cardiac function, and I would arrange the overnight sleep study to screen the respiratory status, because the restrictive respiratory failure is the threat in this disease. I would refer the family to the genetic counsellor, because the collagen VI result sets the inheritance, the prognosis, and the reproductive options. ^[2]