Abstract Introduction Congenital Central Hypoventilation Syndrome (CCHS) is a genetic disorder of the autonomic nervous system caused by mutations in the PHOX2B gene. Children with CCHS often present as neonates in hypoxemic, hypercarbic respiratory failure. Most causative mutations are de novo Polyalanine Repeat Mutations (PARMs). Non-Polyalanine Repeat Mutations (NPARMs) have been associated with more severe disease, specifically the need for 24-hour ventilatory support, Hirschsprung disease, and neural crest tumors; however, NPARMs may have variable expressivity and incomplete penetrance, resulting in delayed or atypical presentations. We report a toddler with maxillary sinus neuroblastoma, which led to the diagnosis of familial PHOX2B NPARM positive CCHS. Report of case(s) A two-year-old boy presented with right-sided facial swelling. A facial CT uncovered a right maxillary sinus lytic lesion, and biopsy confirmed neuroblastoma. After full recovery from the procedure, he had persistent nocturnal hypoxemia and hypercapnia requiring bilevel positive airway pressure (PAP) during sleep, raising concern for CCHS. Genetic testing revealed a novel PHOX2B NPARM, c.428dup, which likely causes a frameshift and premature protein termination (p.Val144Glyfs*34). His maternal grandfather, mother and brothers tested positive for the same mutation. Family history revealed that his maternal grandfather and maternal great-uncles had frequent childhood apneic spells associated with syncope, his maternal grandfather is currently on nocturnal bilevel PAP, and his mother almost drowned as a younger child while having a breath-holding contest under water. His six-year-old brother underwent polysomnography which showed hypoventilation, now managed with bilevel PAP. His five-year-old brother also underwent polysomnography and does not require nocturnal ventilatory support at this time. Conclusion We report a rare case of familial PHOX2B NPARM positive CCHS which initially presented as maxillary sinus neuroblastoma. Additionally, the child and his family display varying disease severity despite having the same NPARM, highlighting the variable expressivity in this novel NPARM. Support (if any) None