Images: Atypical resolution of sleep-related hypoventilation in congenital central hypoventilation syndrome

Paired-like homeobox 2B gene variants cause congenital central hypoventilation syndrome (CCHS) characterized by abnormal ventilatory control necessitating lifelong assisted ventilation (AV). We report a 3-year-old female who presented with apnea, hypoxemia, hypoventilation requiring AV, and Hirschsprung's disease during infancy followed by resolution of hypoventilation. At 3 weeks, polysomnography showed obstructive and central sleep apnea, oxygen desaturations, and hypoventilation. A novel, heterozygous, paternal-inherited 2.77-Mb deletion in chromosome 4p14-p13 resulted in deletion of the entire paired-like homeobox 2B gene, confirming the diagnosis of CCHS. Paired-like homeobox 2B whole-gene deletions are categorized as nonpolyalanine repeat mutations. AV via tracheostomy was utilized during sleep. At 2.8 years, diagnostic polysomnography was performed due to suboptimal adherence to AV that demonstrated central sleep apnea without hypoxemia or hypoventilation. There were no signs of chronic hypoventilation such as polycythemia, elevated serum bicarbonate, or pulmonary hypertension. CCHS is characterized by lifelong hypoventilation requiring AV. Despite a classic presentation of CCHS requiring early tracheostomy, polysomnography at 3 years of age indicated an absence of hypoventilation that represents a unique and atypical presentation in CCHS.

Yoo M, Shah A, Shahrour H, Li H, Kasi AS. Images: Atypical resolution of sleep-related hypoventilation in congenital central hypoventilation syndrome. J Clin Sleep Med. 2025;21(7):1327-1331.