Polysomnographic characteristics and sleep‐disordered breathing in Schaaf‐Yang syndrome

Abstract

Introduction: Schaaf-Yang syndrome (SYS) is a genetic disorder caused by truncating variants in the MAGEL2 gene located in the maternally imprinted Prader-Willi syndrome (PWS) region at 15q11-13. The SYS phenotype shares features with PWS, a syndrome with known high incidence of sleep disorders. However, the spectrum of sleep-disorders in SYS has not been described. Methods: We performed a retrospective analysis of polysomnograms from 22 patients in an international SYS cohort. Sleep characteristics for individuals with the common c.1996dupC variant (n = 10) were compared to other truncating variants (n = 11). Results: We collected 33 sleep study reports from 22 patients, ages 2 months-18.5 years (mean 6.5 years). Mean sleep efficiency was 70.5% (range 45%-93%) with arousal index 14.1/h (1.2-45/h). The mean apnea-hypopnea index (AHI) was 19.1/h (0.9-49/h) with mean obstructive AHI (oAHI) of 16.3/h (0.6-49/h). Mean central apnea index was 2.8/h (0-14/h). Mean oxygen desaturation index was 20.8/h (range 0-85/hr). Obstructive sleep apnea (OSA) was diagnosed in 81%, and 62% had moderate or severe OSA. Elevated central apnea index occurred in 9.5%. Comparison by genotype groups and age did not reveal any difference in OSA findings. Periodic limb movement index (PLMI) was elevated in 4/15 (26%). Conclusion: OSA is frequently identified on polysomnography in patients with SYS. The mean PLMI is elevated compared to normative data. Patients with SYS should have routine polysomnography screening due to high risk of sleep disorders.

Magel2 truncation alters select behavioral and physiological outcomes in a rat model of Schaaf-Yang syndrome

“…Relevant to SYS, fatal cases of congenital heart disease have been reported in MAGEL2 patients ( Chen et al, 2020a ), making these cardiac findings especially relevant. Third, the finding that Magel2 mutant rats experience altered apnea metrics compared to wild-type littermates is interesting when considering elevated rates of obstructive sleep apnea in SYS ( Powell et al, 2020 ). Although respiration was measured in the unrestrained, whole animal during periods of rest to ensure that the breathing measurements were not perturbed by movement, further studies investigating the convergence of sleep behaviors and respiratory performance in these rats would be instructive on breathing abnormalities as surrogate translational markers for SYS and MAGEL2-related disorders.…”

Prader–Willi syndrome: an update

“…Mutations specific to MAGEL2 may be more associated with restless leg syndrome [4,45]. Nonetheless, restless leg syndrome should be investigated in PWS [46].…”

Caregiver‐based perception of disease burden in Schaaf‐Yang syndrome

“…Short stature associated with growth hormone deficiency (GHD) and low bone mineral density as indicators of osteoporosis are observed in most patients; the prevalence of scoliosis is elevated compared to the general population (McCarthy, Lupo, et al, 2018 ; McCarthy, McCann‐Crosby, et al, 2018 ). Additionally, it has been shown that obstructive sleep apnea occurs in most individuals with SYS (Powell et al, 2020 ).…”