Sleep disordered breathing in infants identified through newborn screening with spinal muscular atrophy

Spinal muscular atrophy (SMA) is a genetic disorder that may result in neuromuscular weakness and respiratory insufficiency. Gene replacement therapy has changed the trajectory of this condition, but long-term outcomes related to sleep disordered breathing are not known. This was a retrospective review of infants with SMA identified via newborn screening who subsequently received onasemnogene abeparvovec at the Hospital for Sick Children (Ontario, Canada). Polysomnograms were conducted at the time of confirmed diagnosis as well as regularly thereafter. Eleven children (4 female) were identified via newborn screen (7 with 2 copies of the SMN2 gene and 4 with 3 copies of the SMN2 gene) and received onasemnogene abeparvovec at a median age of 3.6 weeks. All eleven infants met criteria for sleep disordered breathing based on their first completed polysomnograms but improved over time. Three infants required respiratory technology, including a premature infant who was prescribed nocturnal supplemental oxygen therapy for central sleep apnea and two symptomatic infants with neuromuscular weakness who required nocturnal noninvasive ventilation. We did not find a correlation between motor scores and polysomnogram parameters. Children treated with onasemnogene abeparvovec have reduced sleep disordered breathing over time. Polysomnograms revealed abnormal parameters in all children, but the clinical significance of these findings was unclear for children who were asymptomatic for sleep disordered breathing or neuromuscular weakness. These results highlight the need to evaluate both motor scores and respiratory symptoms to ensure a holistic evaluation of clinical status.