Unraveling RYR1 mutations and muscle biopsies

Congenital myopathies present diagnostic challenges in infants and young children since clinical findings alone are rarely distinguishing among the different diseases. Traditional workup for nonprogressive congenital neuromuscular weakness with normal creatine phosphokinase often leads the clinician toward muscle biopsy, hoping for a clear cut pathologic diagnosis. However, much of the time the initial biopsy in young children reveals nonspecific features including fiber type disproportion, type predominance, rarely uniform type 1 fibers, both cores and rods, or even less specific findings. The clinician is thus faced with presenting a best guess to the family, and the option of repeat biopsy at a future date which may or may not reveal a specific diagnosis. Muscle MRI provides further supportive information if a specific pattern of signal abnormality is revealed but usually requires sedation in this age group and rarely leads to a confident diagnosis. Of greater consequence is …