D27-13 Evolving Respiratory Outcomes Following Prenatal Risdiplam Administration in Spinal Muscular Atrophy Type 0: A Case Report

Background Spinal Muscular Atrophy (SMA) type 0 is the most severe and rare form of SMA, typically presenting in utero with decreased fetal movements, joint contractures, profound hypotonia at birth, and early respiratory failure requiring immediate ventilatory support. Historically, SMA type 0 has a poor prognosis, with most infants dying within weeks to months despite maximal supportive care. Early initiation of disease-modifying therapy (DMT), such as onasemnogene abeparvovec, nusinersen, or risdiplam, has changed the landscape for SMA types I-III. However, data for SMA 0 remains extremely limited. Survival beyond six months is rare, and motor milestones are typically absent. We present a case of genetically confirmed SMA 0 treated with prenatal risdiplam, describing postnatal respiratory and neurological outcomes. Clinical Presentation During evaluation of oligohydramnios, both parents were identified as carriers of a single survival motor neuron (SMN) 1 gene deletion. Amniocentesis revealed no copies of SMN1 and one copy of SMN2, confirming SMA type 0. Maternal oral risdiplam therapy was initiated at 28 weeks’ gestation. The infant was delivered at 38 weeks’ gestation via cesarean section (Apgars 6/8). He initially required bubble continuous positive airway pressure (CPAP) and was spontaneously breathing. Physical examination showed global hypotonia, absent reflexes, and bilateral upper-extremity contractures. Due to elevated anti-AAV9 antibody titers, he was ineligible for onasemnogene abeparvovec and continued risdiplam post-natally. He eventually transitioned to bilevel positive airway pressure and subsequently required intubation due to hypercapnia and thoraco-abdominal asynchrony. He experienced recurrent shifting atelectasis and pneumothorax, following early mechanical insufflator/exsufflator use. CXR revealed healed rib fractures. Intrapulmonary percussive ventilation was later tolerated for airway clearance. Neurologically, he demonstrated progressive improvement with spontaneous antigravity movements in both upper and lower extremities (R > L). Long-term ventilatory dependence necessitated tracheostomy. Chest x-ray below at 3 months of life post-tracheostomy. Discussion Neuropathological evidence suggests SMA neurodegeneration begins in utero, supporting prenatal intervention. Recent case report has described the feasibility and potential benefit of prenatal risdiplam therapy on SMA type 1 phenotype This case adds to the limited literature, demonstrating partial neuromotor improvement despite most severe baseline phenotype. While generalization of antenatal therapy is premature, prenatal and continued post-natal use of DMT (risdiplam) may attenuate disease progression and enhance long-term respiratory and neuromuscular outcomes. This case underscores evolving ventilatory and airway-management strategies in the prenatal treatment era for SMA type 0.