Congenital myopathies and muscular dystrophies: Case

Summary and immediate impression

This girl presents a textbook case of merosin-deficient congenital muscular dystrophy from LAMA2. The markedly raised creatine kinase of 6800 units per litre forks the diagnosis toward a congenital muscular dystrophy, and the diffuse white matter abnormality with the structurally normal cortex and the epilepsy lands it on the merosin-deficient form, because the laminin-alpha-2 chain is expressed in the white matter and the nerve as well as the muscle. The alert baby with the spared cognition fits the form, and the immediate threats are the respiratory failure and the seizures. [1][5]

The diagnostic approach

I would 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 6800 units per litre is markedly raised, which forks the diagnosis toward a congenital muscular dystrophy and away from a congenital myopathy or a mimic such as spinal muscular atrophy, in which the kinase is normal or only mildly raised. The markedly raised kinase raises the merosin-deficient and the dystroglycanopathy forms above the collagen VI and the LMNA forms, which carry a normal or mildly raised kinase. [1]

The brain magnetic resonance imaging refines the diagnosis. The diffuse white matter abnormality with the structurally normal cortex points to the merosin-deficient form, and I would contrast this with the cobblestone lissencephaly and the eye malformations of the dystroglycanopathies such as Walker-Warburg syndrome, in which the abnormal cortex and the eye change define the syndrome and set the grimmest prognosis. The epilepsy in this girl fits the merosin-deficient form, in which around a third of the children have seizures, while the cognition is typically spared. [9]

I would confirm the diagnosis with the next-generation sequencing muscle panel targeting LAMA2 alongside the other major congenital-muscle-disease genes, and I would add the nerve conduction studies, which may show the demyelinating peripheral neuropathy of the merosin-deficient disease. I would reserve the muscle biopsy with the merosin immunohistochemistry for the panel-negative case. I would complete the baseline with the echocardiogram and the electrocardiogram to screen the cardiac function and the overnight sleep study to screen the respiratory status, because the restrictive respiratory failure is the threat. [1][10]

Management over the first year

The management is the multidisciplinary supportive care, because there is no curative therapy for the merosin-deficient disease. The respiratory management is the part that changes the survival, and I would track the forced vital capacity and the overnight sleep study at least annually and start the nocturnal non-invasive ventilation for the objective nocturnal hypoventilation, because it is the single intervention that most extends the life. I would add the cough assistance with the mechanical insufflation-exsufflation device to prevent the chest infections that drive the acute deterioration. The nutritional management runs alongside: I would secure the feeding with the nasogastric tube and plan the gastrostomy to prevent the failure to thrive and to secure the medication route. [2]

The orthopaedic and the seizure management complete the first year. 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, and I would start the antiseizure medicine for the epilepsy under the neurology guidance. Corticosteroids, I would note, have no established role in the merosin-deficient disease, in contrast to their role in Duchenne muscular dystrophy. [2]

Prognosis, counselling, and follow-up

I would tell the family that this is merosin-deficient congenital muscular dystrophy from LAMA2, inherited in an autosomal recessive pattern, and that the child carries a survival into adolescence and adulthood with the respiratory and the orthopaedic support. I would be honest that the child rarely achieves the independent walking, that the restrictive respiratory failure is the expected complication, and that the seizures are usually controllable, while the cognition is typically spared despite the white matter change. I would give the family the genetic counselling and the prenatal diagnosis for the future pregnancies, because the autosomal recessive recurrence risk is 25 percent. [1][10]

I would arrange the regular surveillance with the neuromuscular clinic, the respiratory function tests, and the sleep studies, and I would plan the transition to the adult neuromuscular service from the early teenage years. I would give the family the safety-net for the respiratory deterioration and the seizure breakthrough, and I would coordinate the school and the community services, because the multidisciplinary care and the family support are part of the treatment, not an afterthought. [2]

Marking domains

• Diagnosis and reasoning: uses the creatine kinase fork and the white matter pattern to land on the merosin-deficient LAMA2 form and distinguishes it from the dystroglycanopathies and the collagen VI form. [1]
• Management — resuscitation and definitive: secures the feeding and starts the respiratory surveillance with the sleep study and the forced vital capacity and the multidisciplinary care. [2]
• Complications and surveillance: monitors the respiratory failure, the contractures and the scoliosis, and the seizures. [2]
• Communication: counsels the family on the autosomal recessive inheritance, the prognosis with the spared cognition, and the prenatal diagnosis for the future pregnancies. [10]