B61-15 Congenital Myasthenic Syndrome: A Rare Etiology of Persistent Ventilator Dependence in Neonates

Abstract Introduction Congenital myasthenic syndrome (CMS) represents a rare and likely underrecognized cause of respiratory failure in infancy. In this case series, we describe two infants with prolonged admissions to the NICU with multiple failed extubations and subsequent tracheostomy and mechanical ventilator dependence. They were ultimately diagnosed with CMS due to mutation of the choline acetyltransferase (CHAT) enzyme, which accounts for approximately 4-5% of CMS cases. Case In case 1, we present a former term infant male born via C-section, admitted to the NICU intubated due to acute hypoxemic respiratory failure in the setting of hypoxic ischemic encephalopathy (HIE). He had failed two extubation trials due to increased respiratory effort and hypercapnic respiratory failure prior to pediatric pulmonary consultation and required ongoing ventilator support without supplemental oxygen. Chest CT demonstrated normal lung parenchyma and patent airways. A transthoracic echocardiogram was normal. His airway evaluation revealed dynamic bilateral tracheobronchomalacia and mild subglottic narrowing requiring dilation. The patient had six total failed extubations prior to tracheostomy on day of life 145. Rapid exome sequencing by genetics ultimately revealed biallelic mutation of the CHAT gene - CHAT c.406GA (p.V136M) and CHAT c.1510CT (p.R504) - yielding loss of function in the CHAT enzyme that synthesizes acetylcholine and consequent defective signaling at the neuromuscular junction. This confirmed a diagnosis of congenital myasthenic syndrome as the etiology of his respiratory failure. In case 2, we present a former term infant female born via C-section secondary to non-reassuring fetal status, also admitted to the NICU with HIE. Similarly to case 1, she was intubated shortly following delivery. She had recurrent failed extubation attempts due to apneic episodes with an otherwise unrevealing workup including brain and chest imaging. There was initial concern for upper airway obstruction due to findings of glottic granulation tissue on her otherwise normal airway evaluation. However, despite granulation tissue removal and subglottic dilation, she eventually underwent tracheostomy placement on day of life 69 after five total failed extubations. She was ultimately found to have homozygous mutation of the CHAT gene c.406GA (p.V136M) causing CMS and tracheostomy-ventilator dependence as in case 1. Discussion These cases exhibit the diagnostic challenge of CMS and highlight opportunities for advancement in the field. We hope that earlier recognition of these rare mutations and their presentation with neuromuscular weakness causing respiratory failure in infancy would better inform treatment plans and allow for prevention of delayed diagnosis. This abstract is funded by: None