Effects of Growth Hormone Therapy on Sleep-Disordered Breathing and Metabolic Parameters in Patients with Prader–Willi Syndrome According to Genetic Subtype

<title>Abstract</title> <p>Objective Prader–Willi syndrome (PWS) is frequently associated with sleep-disordered breathing, and the respiratory effects of recombinant human growth hormone (rhGH) therapy are debated. This study assessed the anthropometric, metabolic, and polysomnographic outcomes of rhGH therapy in children with PWS and investigated whether these outcomes varied according to molecular subtype. Methods This retrospective cohort study included 66 children with genetically confirmed PWS who received rhGH therapy for a minimum of 12 months. Patients were classified as having either a paternal 15q11–q13 deletion or maternal uniparental disomy (mUPD); deletion cases were further categorized as type I, type II, or atypical. Anthropometric and metabolic parameters were measured at baseline and after 12 months. Polysomnography was conducted prior to treatment and repeated after 3–6 months. Longitudinal polysomnographic analyses included 39 patients with a baseline apnea–hypopnea index (AHI) less than 5 events per hour who did not require additional respiratory intervention. Results The median age at initiation of treatment was 3.53 years, with 32 patients (49%) identified as female. Forty-five patients (68.3%) exhibited a paternal deletion. After 12 months, the height standard deviation score increased significantly (P &lt; 0.001), while weight and body mass index standard deviation scores did not change significantly. Glucose and lipid parameters remained stable. In the longitudinal polysomnographic analysis, both total AHI and obstructive AHI increased significantly during the first 3–6 months of treatment, primarily among patients with deletions rather than those with mUPD. Within the deletion group, patients with type II deletions demonstrated significant increases in both total and obstructive AHI, whereas no significant longitudinal deterioration was observed in patients with type I deletions. Conclusion After one year of rhGH therapy, linear growth improved without adversely affecting short-term metabolic outcomes in children with PWS. However, early obstructive respiratory events increased, particularly among patients with type II deletions. These findings indicate that molecular subtype may influence the respiratory response to rhGH and support the need for close polysomnographic monitoring during the initial six months of treatment.</p>