Publication Date

6-2025

Download

Download Full Text (540 KB)

Abstract

Introduction Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder caused by the mutation of the paired-like homeobox 2B (PHOX2B) gene that leads to alveolar hypoventilation during sleep and at times while awake. The majority of patients with CCHS have polyalanine repeat mutations (PARM) whereas 10% have non-PARM (NPARM). Of those with NPARM, less than 1% are caused by whole gene deletion. NPARM is associated with more severe phenotypes; however, some may have variable penetrance causing variable presentation within families. Report of case(s) Our patient is a 4-month-old infant born at 32 weeks in an outside hospital and transferred to our tertiary NICU at 10 weeks of age due to feeding difficulties, respiratory distress, hypoxemia, macroglossia and concern for Beckwith-Wiedemann syndrome. Upon transfer, she was on 2L of oxygen (FiO2: 0.3) via high flow nasal cannula. During her stay, she was noted to have hypoventilation which was thought to be secondary to upper airway obstruction. Upper airway evaluation by ENT revealed mild laryngomalacia for which supraglottoplasty was performed. Drug induced sleep endoscopy (DISE) revealed macroglossia with posterior displacement of the epiglottis causing obstruction. Due to concerns for obstruction and persistent hypoxemia, she was referred for a polysomnogram (PSG). The study was started on room air, but 1/4L of oxygen via low flow nasal cannula (LFNC) was initiated after 6 minutes due to persistent hypoxemia and hypoventilation. PSG showed an apnea hypopnea index (AHI) of 18/hour, central apnea index (CAI) of 11/hour with persistent nocturnal hypoventilation based on ETCO2, transcutaneous CO2 monitor (TCM) and blood gas (ETCO2 > 50mmHg for 85% of total sleep time (TST), max ETCO2: 62mmHg, TCM>50mmHg for 96% TST, peak TCM: 70mmHg). Given these findings, recommendations were made to obtain PHOX2B gene testing and obtain neurologic workup. Exome sequencing showed deletion of the PHOX2B gene consistent with CCHS. Conclusion A high suspicion for CCHS should be present in patients with central apnea and hypoventilation. Many children with CCHS may be missed due to complex genetic testing and variation in clinical presentation.

Disciplines

Pediatrics | Sleep Medicine

Notes

Presented at the SLEEP 2025 Annual Meeting; June 8-11, 2025; Seattle, Washington.

When Macroglossia is not Beckwith-Wiedemann: A Case of an Infant with Congenital Central Hypoventilation Syndrome

Share

COinS