1037 WORTH A SECOND LOOK: A Case of an Infant with NPARM CCHS with a Negative PSG and Normal PHOX2B

INTRODUCTION Congenital Central Hypoventilation Syndrome is a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation. A PHOX2B gene mutation is required to confirm the diagnosis of CCHS. REPORT OF CASE A male term infant born to a 21-year-old primigravid without prenatal complications presented at 4 weeks old with cyanosis and apnea. Work-up showed hypoglycemia and leukocytosis. He was intubated and given antibiotics for 7 days. He had persistent witnessed apneas post-extubation, despite bilevel PAP support. Brain ultrasound and MRI, EEG, echocardiography were reportedly normal. Patient was transferred to our institution and re-intubated. He presented with fever, nasal congestion and intermittent stridor. He was started on empiric antibiotics and was extubated after a week. Initial PSG done at 6 weeks of age showed moderate OSA (AHI 11.7. RDI 11.2) with elevated pCO2 (highest 53mmHg), with 3 central apneas (CAI 0.5). Impression was Apnea and Acute Respiratory Failure due to likely viral infection. Patient was discharged home on room air with oral prednisone. Genetic testing was pending at discharge. Patient was asymptomatic when genetic tests were resulted. PHOX2B gene test (RUSH Medical Laboratories) was normal with 20 repeats/allele. Critical Trio Whole Exome Sequencing (Baylor Genetics) showed a heterozygous c.945A>C (p.*315Cext*41) pathogenic NPARMs in the PHOX2B gene. WES showed that the mother is negative and father possibly mosaic for this change. Repeat polysomnography at 11 weeks old showed severe OSA (AHI 135, RDI 135, with 122 obstructive events/hour) with oxygen nadir 70% and Moderate CSA (CAI 12.7) with severely elevated PCO2 values (highest at 76mmHg). Positive airway pressure (up to 14/4 cmH2O) with a back-up rate of 25cpm and supplemental oxygen at 1Lpm improved the obstructive events, however patient continued to have hypoventilation. He was placed on bilevel PAP during PICU re-admission. A tracheostomy tube was placed for long-term mechanical ventilation. He was discharged home with family at 19 weeks of age and has been doing well since. CONCLUSION ~10% of CCHS patients have non-polyalanine repeat mutations (NPARMs), which is associated with a more severe phenotype. We present an atypical presentation of a rare disease: NPARM CCHS in which the initial PSG did not demonstrate hypoventilation, and initial PHOX2B test was normal. Our case shows that close clinical monitoring and extended genetics should be consi