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]

Question 2 (10 marks)

Discuss your management plan, the complications you would monitor for, and the prognosis and follow-up you would discuss with the family. [2]

The management is the multidisciplinary supportive care, because there is no curative therapy for the collagen VI disease, and the disease-modifying landscape is still emerging. The respiratory management is the part that changes the survival, and the hallmark of the collagen VI disease is the restrictive respiratory failure that develops while the child is still walking, so I would track the forced vital capacity seated and supine and the overnight sleep study at least annually. I would start the nocturnal non-invasive ventilation for the objective nocturnal hypoventilation or the symptomatic daytime sleepiness, because it is the single intervention that most extends the life, and I would add the cough assistance with the mechanical insufflation-exsufflation device to prevent the chest infections that drive the acute deterioration. [2]

The nutritional and the orthopaedic management run alongside. I would secure the feeding with the nasogastric tube now and plan the gastrostomy to prevent the failure to thrive and to secure the medication route. I would manage the contractures with the passive stretching, the splinting, and the serial casting, and I would monitor the scoliosis with the spinal radiograph, with the spinal fusion reserved for the progressive and severe curve. I would involve the physiotherapy, the occupational therapy, and the rehabilitation teams, because the management is a lifelong process. [2][3]

I would tell the family that this is a collagen VI-related congenital muscular dystrophy, that the child will likely achieve some walking but that the restrictive respiratory failure is the expected complication, and that the nocturnal ventilation and the multidisciplinary care carry the survival into adulthood. I would be honest that the weakness is lifelong, that the respiratory dependence may reshape the daily life, and that the cyclosporin analogue that targets the mitochondrial permeability transition pore is under clinical investigation. I would give the family the genetic counselling and the prenatal diagnosis for the future pregnancies, and I would arrange the transition planning to the adult neuromuscular service from the early teenage years. [2][8]