Association between upper airway obstruction and pulmonary hypertension in children with Down syndrome.

PURPOSE OF REVIEW: Down syndrome (DS) is the most common nonlethal chromosomal aneuploidy, affecting 1 in 700 live births. Pulmonary hypertension (PH) occurs in approximately 25% of children with DS and contributes to a 10% mortality rate within 3  years of diagnosis. Despite obstructive sleep apnea (OSA) affecting up to 80% of children with DS, the specific contribution of upper airway obstruction to PH in this population remains poorly characterized. This review synthesizes current evidence to address that gap.

RECENT FINDINGS: Children with DS develop multilevel upper airway obstruction due to craniofacial dysmorphology, relative macroglossia, hypotonia, and reduced peripheral chemosensitivity. OSA-driven chronic hypoxemia promotes pulmonary vascular remodeling, with 87% of recurrent PH cases classified as WHO Group III. Echocardiographic diagnosis is limited by chronic lung disease. NT-proBNP is the most reliable biomarker in DS. Adenotonsillectomy reduces apnea severity, though evidence of a reduction in mean pulmonary arterial pressure in DS is lacking. Endothelin receptor antagonists show functional benefit, while sildenafil appears less effective in DS-specific analyses.

SUMMARY: No DS-specific PH staging system exists, representing a critical gap. Future research should quantify the impact of airway interventions on pulmonary hemodynamics, develop DS-tailored biomarkers, and optimize pharmacologic regimens in this molecularly distinct population.