A term newborn is diagnosed with multiple congenital contractures. The infant has symmetric, rigid contractures of all four limbs, with internally rotated shoulders, extended elbows, and severe equinovarus foot deformities. There is a marked decrease in limb muscle mass but normal central nervous system function and no family history of similar conditions. What is the most likely diagnosis for this infant?
A 7-year-old boy with a known diagnosis of spinal muscular atrophy type III is able to walk independently but has progressive proximal weakness. In addition to weakness, which of the following is a specific clinical sign of muscle denervation that can often be observed in the tongue?
A neonate is born with severe generalized weakness, respiratory failure, and arthrogryposis (fetal akinesia deformation sequence). A muscle biopsy shows characteristic rod-like structures. Genetic testing is pursued to identify the underlying cause. Pathogenic variants in which of the following proteins account for more than half of the severe neonatal cases of nemaline rod myopathy?
A 9-year-old child presents with acute onset of external ophthalmoplegia, ataxia, and areflexia following a recent respiratory infection. Lower extremity strength is preserved. Which variant of Guillain-Barré syndrome best describes this presentation?
A 3-year-old child presents with a floppy infant history and now shows progressive limb and bulbar weakness, leading to respiratory failure requiring non-invasive ventilation. Laboratory workup reveals an elevated creatine kinase and a high plasma lactate level. A mitochondrial depletion syndrome is suspected. Pathogenic variants in which gene are associated with this specific myopathic subgroup of mtDNA maintenance defect, for which treatment with pyrimidine deoxynucleosides is a potential therapy?
A 7-year-old is undergoing a diagnostic muscle biopsy for a suspected congenital myopathy. The surgeon is deciding on the best site to sample. Which muscle is generally avoided for biopsy because its normal fiber-type predominance can make interpretation difficult?
A neonate is born with severe hypotonia, arthrogryposis, and seizures. A brain MRI reveals cobblestone lissencephaly. A muscle biopsy confirms a muscular dystrophy, and the serum creatine kinase level is high. This combination of severe congenital muscular dystrophy and brain malformation is most characteristic of defects in the glycosylation of which protein?
A newborn male presents with severe generalized hypotonia, respiratory distress, and clubfoot deformities. His mother, who had polyhydramnios during pregnancy, has mild facial weakness and difficulty releasing her grip. What is the most likely genetic mechanism underlying the infant’s severe presentation?
A 10-year-old is being evaluated for myotonia. To differentiate the underlying channelopathy, the physician asks the child to forcefully close and open their eyes repeatedly. With each repetition, the task becomes progressively more difficult. This finding of worsening myotonia with exercise is characteristic of a disorder affecting which type of ion channel?
A 14-year-old boy presents with a history of slowly progressive weakness in a scapulohumeroperoneal distribution. He has developed prominent contractures of his elbows and ankles. His family is concerned about a history of sudden cardiac death in a maternal uncle. Which of the following is the most critical investigation to perform regularly in this patient?