Phenotypic heterogeneity and management of sleep-disordered breathing in children with Prader-Willi syndrome

Introduction: Sleep-disordered breathing (SDB) in children with Prader-Willi syndrome (PWS) is complex and heterogeneous, contributing to morbidity and complicating management. Aim: To retrospectively analyze the spectrum of SDB phenotypes and therapeutic approaches in a cohort of PWS patients. Methods: Thirty-one patients (16 girls, 15 boys) were included. Data comprised phenotypic features, polysomnography, transcutaneous capnometry, and treatment modalities. Evaluation for SDB was initiated just after genetic diagnosis. Growth hormone (GH) was started only after SDB evaluation in the absence of severe obstructive SDB; in such cases treatment was suspended until adenotonsillectomy and improvement of sleep study parameters. Results: Central apnea with cAHI>5/h was corrected in three infants during the first year of life with long-term oxygen therapy. In one six-year-old girl, oxygen plus acetazolamide resolved central events. Severe obstructive SDB (AHI>10/h) was identified in 10 patients; six showed nocturnal hypoventilation. Adenotonsillectomy was performed in six, but due to persistent symptoms in two and absent surgical indication in four, NIV was initiated at home (mean age 10.2 years). Nine children, including four on NIV, were extremely obese (BMI>3 SD). GH was resumed in three patients after SDB resolution and BMI improvement, whereas in three with NIV it was permanently discontinued due to worsening obesity. Conclusion: While early age was associated with central SDB, older age, extreme obesity, and delayed GH initiation predicted long-term NIV need. Early phenotypic stratification and timely respiratory workup are crucial to optimize outcomes in children with PWS.