B61-16 Unmasking Musk: Neonatal Respiratory Failure Revealing a Rare Congenital Myasthenic Syndrome

Introduction Congenital Myasthenic Syndromes are uncommon causes of neuromuscular junction failure in newborns and children. They are caused by genetic defects in presynaptic, synaptic basal lamina, and postsynaptic components of the neuromuscular junction (NMJ). Congenital Myasthenic Syndromes are caused by genetic variants in several genes including primary acetylcholine receptor (AChR) deficiency (the most frequent type), RAPSN, COLQ and DOK7, among others. We present a case of a neonate found to have congenital myasthenic syndrome (CMS) caused by variants in the MUSK gene which was only first reported in 2004 with only 23 cases worldwide reported since 2020. Case Description This is a 3-month-old male born at 37 + 4/7 weeks to a G8P1061 31-year-old mother via emergency cesarean section under general anesthesia due to non-reassuring fetal heart rate complicated by uterine rupture who was admitted for suspected hypoxemic- ischemic encephalopathy and respiratory distress. He was intubated on day of life 1 for worsening respiratory failure and extubated 6 days later. However, he did not tolerate extubation and was re-intubated the next day. Two days later, he was successfully extubated to continuous positive airway pressure. Given maternal history of multiple pregnancy losses and a prior fetus with anencephaly, genetics was consulted. A whole genome sequence was done which revealed gene variants in the MUSK gene pointing to a diagnosis of Congenital Myasthenic Syndrome 9 (CMS9). An electromyography was performed which was consistent with a severe post-synaptic NMJ disorder. Although he initially showed some improvement in his respiratory status with use of an enteral β2- agonist, he ultimately required tracheostomy and mechanical ventilation for chronic respiratory insufficiency. On subsequent outpatient follow-up, patient is doing well on home ventilation and has been tolerating in-line heat moisture exchanger during the day. Discussion CMS9 is caused by loss-of-function variants in the MUSK gene, which encodes the Muscle Associated Receptor Tyrosine Kinase (MuSK). MuSK plays an integral role in aggregating acetylcholine receptors at the post-synaptic membrane of the NMJ, a process essential for effective neuromuscular transmission. Although post-synaptic CMS is associated with poor response to cholinesterase inhibitors, several reports have described a favorable response to β2-adrenergic receptor agonists, which can enhance muscle strength and improve motor function. Given the significant respiratory muscle involvement often observed in CMS9, patients may develop chronic respiratory insufficiency and require long-term ventilatory support. Careful assessment of respiratory function and early consideration of home mechanical ventilation are essential to optimize long-term outcomes and quality of life. This abstract is funded by: None