Background Nonsense and frameshift mutations in the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader-Willi critical region 15q11-15q13, have been reported to cause Schaaf-Yang syndrome (SYS), a genetic disorder that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties and autism spectrum disorder. Prader-Willi syndrome (PWS) is a genetic disorder characterised by severe infantile hypotonia, hypogonadotrophic hypogonadism, early childhood onset obesity/hyperphagia, developmental delay/intellectual disability and short stature. Scoliosis and growth hormone insufficiency are also prevalent in PWS.
There is extensive documentation of the endocrine and metabolic phenotypes for PWS, but not for SYS. This study served to investigate the hormonal, metabolic and body composition phenotype of SYS and its potential overlap with PWS.
Methods In nine individuals with SYS (5 female/4 male; aged 5–17 years), we measured serum ghrelin, glucose, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3, follicle-stimulating hormone, luteinising hormone, thyroid-stimulating hormone, free T4, uric acid and testosterone, and performed a comprehensive lipid panel. Patients also underwent X-ray and dual-energy X-ray absorptiometry analyses to assess for scoliosis and bone mineral density.
Results Low IGF-1 levels despite normal weight/adequate nutrition were observed in six patients, suggesting growth hormone deficiency similar to PWS. Fasting ghrelin levels were elevated, as seen in individuals with PWS. X-rays revealed scoliosis >10° in three patients, and abnormal bone mineral density in six patients, indicated by Z-scores of below −2 SDs.
Conclusion This is the first analysis of the hormonal, metabolic and body composition phenotype of SYS. Our findings suggest that there is marked, but not complete overlap between PWS and SYS.
- bone mineral density
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Contributors JMMcC performed the study and data analysis, and wrote the initial version of the manuscript. BMMcC-C participated in conceiving the study, and edited the manuscript. MER edited the manuscript and re-analysed the data. JY analysed data and generated figures. C-AC participated in performing the study. MAA participated in performing the study. HTNN analysed data. JLM provided guidance in study design, interpreted data and edited the manuscript. CPS conceived the study, supervised the study, acquired funding and edited the manuscript.
Funding This study was supported by the Foundation for Prader-Willi Research, and NIH grant U54HD08302 (IDDRC, Clinical Translational Core).
Competing interests None declared.
Ethics approval Baylor College of Medicine, IRB.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement There are no additional, unpublished data from the study.