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Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome.
J Med Genet. 2018 05; 55(5):307-315.JM

Abstract

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.

Authors+Show Affiliations

Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA.Division of Endocrinology, Department of Pediatrics, Texas Children's Hospital, Houston, Texas, USA.Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA.Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA.Division of Radiology, Texas Children's Hospital, Houston, Texas, USA.Division of Endocrinology, Department of Pediatrics, University of Florida, Gainesville, Florida, USA.Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29496979

Citation

McCarthy, John M., et al. "Hormonal, Metabolic and Skeletal Phenotype of Schaaf-Yang Syndrome: a Comparison to Prader-Willi Syndrome." Journal of Medical Genetics, vol. 55, no. 5, 2018, pp. 307-315.
McCarthy JM, McCann-Crosby BM, Rech ME, et al. Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome. J Med Genet. 2018;55(5):307-315.
McCarthy, J. M., McCann-Crosby, B. M., Rech, M. E., Yin, J., Chen, C. A., Ali, M. A., Nguyen, H. N., Miller, J. L., & Schaaf, C. P. (2018). Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome. Journal of Medical Genetics, 55(5), 307-315. https://doi.org/10.1136/jmedgenet-2017-105024
McCarthy JM, et al. Hormonal, Metabolic and Skeletal Phenotype of Schaaf-Yang Syndrome: a Comparison to Prader-Willi Syndrome. J Med Genet. 2018;55(5):307-315. PubMed PMID: 29496979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome. AU - McCarthy,John M, AU - McCann-Crosby,Bonnie M, AU - Rech,Megan E, AU - Yin,Jiani, AU - Chen,Chun-An, AU - Ali,May A, AU - Nguyen,HaiThuy N, AU - Miller,Jennifer L, AU - Schaaf,Christian P, Y1 - 2018/03/01/ PY - 2017/09/01/received PY - 2017/12/20/revised PY - 2018/01/06/accepted PY - 2018/3/3/pubmed PY - 2019/9/24/medline PY - 2018/3/3/entrez KW - MAGEL2 KW - IGF-1 KW - bone mineral density KW - ghrelin KW - scoliosis SP - 307 EP - 315 JF - Journal of medical genetics JO - J. Med. Genet. VL - 55 IS - 5 N2 - 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. SN - 1468-6244 UR - https://www.unboundmedicine.com/medline/citation/29496979/Hormonal_metabolic_and_skeletal_phenotype_of_Schaaf_Yang_syndrome:_a_comparison_to_Prader_Willi_syndrome_ L2 - http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=29496979 DB - PRIME DP - Unbound Medicine ER -