Congenital myopathies and muscular dystrophies: Viva

Branch 1: The creatine kinase as the first fork

A strong candidate recognises that the alert but weak baby with absent reflexes has a neuromuscular cause of the floppy infant, and that the creatine kinase is the single highest-yield first test. The 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]

Branch 2: The brain imaging forks the muscular dystrophies

When the examiner asks how the imaging refines the diagnosis, the candidate uses the diffuse white matter abnormality with the structurally normal cortex to land on merosin-deficient congenital muscular dystrophy from LAMA2. The laminin-alpha-2 chain is expressed in the white matter and the peripheral nerve as well as the muscle, which explains the white matter change, the demyelinating neuropathy, and the epilepsy, while the cognition is typically spared. The candidate contrasts this with the cobblestone lissencephaly and the eye malformations of the dystroglycanopathies such as Walker-Warburg syndrome, in which the over-migration of the neurons past the cortical surface produces the abnormal cortex that defines the syndrome, and the prognosis is set by the brain malformation. [1][9]

Branch 3: Confirming the gene

When asked how the candidate confirms the diagnosis, the answer is the next-generation sequencing muscle panel, which has replaced the muscle biopsy as the first-line diagnostic test, because it is faster, less invasive, and identifies the gene in the majority. The panel targets the major genes LAMA2, COL6A1 to COL6A3, the dystroglycanopathy genes, LMNA, SEPN1, TTN, RYR1, NEB, ACTA1, MTM1, and DNM2. The muscle biopsy with the immunohistochemistry for merosin is reserved for the panel-negative case or when the histological pattern is itself the question. The nerve conduction studies may show the demyelinating neuropathy of the merosin-deficient disease. [1][10]

Branch 4: The management ladder

When the examiner asks how the candidate runs the management, the answer is the multidisciplinary supportive care built around the four complications that dominate the course: the respiratory failure, the feeding difficulty, the contractures and the scoliosis, and the epilepsy. The respiratory management is the part that changes the survival, and the candidate tracks the forced vital capacity and the overnight sleep study at least annually and starts the nocturnal non-invasive ventilation for the objective hypoventilation. The gastrostomy secures the nutrition and the medication route, and the stretching and the splinting manage the contractures. Corticosteroids, the candidate notes, have no established role in the non-dystrophin congenital muscular dystrophies, in contrast to their role in Duchenne muscular dystrophy. [2]

Branch 5: The malignant hyperthermia pitfall

The examiner then offers a different child with the central core disease on the biopsy and the RYR1 mutation, and the candidate names the malignant hyperthermia risk as the life-threatening association. The ryanodine receptor that forms the cores is the same calcium release channel that leaks the uncontrolled calcium in response to the volatile anaesthetics and the succinylcholine, and the crisis is prevented by the avoidance and treatable by the dantrolene. The candidate flags the family, issues the medic-alert, and plans the trigger-free anaesthetic technique, and stresses that this is the pitfall that the management must prevent. [11]

Branch 6: Prognosis and the family

Asked what to tell the family, the candidate quotes that the merosin-deficient form carries a survival into adolescence and adulthood with the respiratory and the orthopaedic support, that the child rarely achieves the independent walking, and that the cognition is usually spared despite the white matter change. The candidate is honest that the weakness is lifelong, that the restrictive respiratory failure is the expected complication, and that the multidisciplinary care carries the trajectory. The candidate gives the family the genetic counselling and the prenatal diagnosis for the autosomal recessive recurrence, because the LAMA2 result sets the recurrence risk. The examiner rewards a candidate who sends the creatine kinase first, who forks the muscular dystrophies on the brain imaging, who confirms the gene with the panel, who runs the multidisciplinary management, and who flags the malignant hyperthermia and the cardiac risks. [1][2]