Abstract
Aim The diagnostic workup in patients with delayed motor milestones suspected of having
either myopathy or a congenital myasthenic syndrome is complex. Our hypothesis was
that performance of a muscle biopsy and neurophysiology including stimulated single-fiber
electromyography during an anesthetic procedure, combined with genetic testing has
a high diagnostic quality.
Materials and Methods Clinical and paraclinical data were retrospectively collected from 24 patients aged
from 1 month to 10 years (median: 5.2 years).
Results Neurophysiology examination was performed in all patients and was abnormal in 11
of 24. No patients had findings suggestive of a myasthenic syndrome. Muscle biopsy
was performed in 21 of 24 and was normal in 16. Diagnostic findings included nemaline
rods, inclusion bodies, fiber size variability, and type-II fiber atrophy. Genetic
testing with either a gene panel or exome sequencing was performed in 18 of 24 patients,
with pathogenic variants detected in ACTA1, NEB, SELENON, GRIN2B, SCN8A, and COMP genes.
Conclusion Results supporting a neuromuscular abnormality were found in 15 of 24. In six patients
(25%), we confirmed a genetic diagnosis and 12 had a clinical neuromuscular diagnosis.
The study suggests that combined use of neurophysiology and muscle biopsy in cases
where genetic testing does not provide a diagnosis can be useful in children with
delayed motor milestones and clinical evidence of a neuromuscular disease.
Keywords
children - diagnostic yield - muscle biopsy - neuromuscular disorders - single fiber
electromyography
