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Introduction Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder characterized by hypotonia, behavioral problems, endocrinopathies, sleep and respiratory abnormalities. Morbidity and mortality in the PWS population is attributable to obesity, cardiovascular problems, and sleep apnea. We report a patient with PWS presenting with pulmonary arterial hypertension (PAH) due to untreated obstructive sleep apnea (OSA). Report of case(s) Our patient is a 17-year-old female with a past medical history of PWS, scoliosis, obesity (BMI 52.46), hypogonadotropic hypogonadism, and type II diabetes. Baseline echocardiogram (ECHO) performed at age 9 revealed an estimated right ventricular systolic pressure (eRVSP) of 32mmHg above right atrial pressure (RAP), tricuspid regurgitation (TR) at 2.8 m/sec with no interventricular septal flattening (IVSF) and right ventricle (RV) systolic dysfunction suggestive of mild PAH. Given significant scoliosis the patient did not qualify for growth hormone therapy. She underwent a polysomnogram (PSG) at age 14 showing severe obstructive sleep apnea; apnea-hypopnea index (AHI) of 22.6 (oAHI 22.6). Patient was subsequently lost to follow up until presenting in acute respiratory failure at age 17. She required endotracheal intubation and was extubated to bilevel PAP (BPAP) with inability to wean off BPAP. At that time an ECHO revealed eRVSP of 55 mmHg above RAP, IVSF, TR at 3.7 m/sec, and RV systolic dysfunction suggestive of moderate to severe PAH and developing right sided heart failure. A PAP titration PSG during this admission revealed hypoxemia with oxygen saturation less than 90% (O2 nadir 70%) 12.6% of total sleep time (TST) and hypoventilation (transcutaneous CO2 max of 57 mmHg with an elevation above 50 mmHg for 100% of TST). Using an inspiratory PAP (IPAP) of 24 cmH2O and expiratory PAP (EPAP) of 14 cmH20 with supplemental O2 of 4LPM the respiratory events and hypoxemia resolved but there was persistence of hypoventilation. Tadalafil was initiated for PAH and BPAP therapy for OSA. Follow up visits 4- and 8-weeks post discharge shows improving PAH (TR 3.6 m/sec, eRSVP 52 mmHg, and mild IVSF) due to BPAP and tadalafil therapies. Conclusion This case highlights the importance of treating OSA in patients with PWS to prevent cardiorespiratory complications and reduce morbidity and mortality. Support (if any) None

Potocki-Lupski syndrome (PTLS; MIM 610883) is a neurodevelopmental disorder caused by a microduplication, a 3.7 Mb copy number variant, mapping within chromosome 17p11.2, encompassing the dosage-sensitive RAI1 gene. Whereas RAI1 triplosensitivity causes PTLS, haploinsufficiency of RAI1 due to 17p11.2 microdeletion causes the clinically distinct Smith-Magenis syndrome (SMS; MIM 182290). Most individuals with SMS have an inversion of the melatonin cycle. Subjects with PTLS have mild sleep disturbances such as sleep apnea with no melatonin abnormalities described. Sleep patterns and potential disturbances in subjects with PTLS have not been objectively characterized. We delineated sleep characteristics in 23 subjects with PTLS who underwent a polysomnogram at Texas Children's Hospital. Eleven of these subjects (58%) completed the Child's Sleep Habits Questionnaire (CSHQ). Urinary melatonin was measured in one patient and published previously. While the circadian rhythm of melatonin in PTLS appears not to be disrupted, we identified significant differences in sleep efficiency, percentage of rapid eye movement sleep, oxygen nadir, obstructive apnea hypopnea index, and periodic limb movements between prepubertal subjects with PTLS and previously published normative data. Data from the CSHQ indicate that 64% (7/11) of parents do not identify a sleep disturbance in their children. Our data indicate that younger individuals, <10 years, with PTLS have statistically significant abnormalities in five components of sleep despite lack of recognition of substantial sleep disturbances by parents. Our data support the contention that patients with PTLS should undergo clinical evaluations for sleep disordered breathing and periodic limb movement disorder, both of which are treatable conditions. K E Y W O R D S duplication 17p11.2, Potocki-Lupski syndrome, sleep