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.
J Med Genet. 2018 May;55(5):307-315. doi: 10.1136/jmedgenet-2017-105024. Epub 2018 Mar 1.
Nonsense and frameshift mutations in the maternally imprinted, paternally expressed gene 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.
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.
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.
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.
位于 Prader-Willi 关键区域 15q11-15q13 的母系印迹、父系表达基因中无意义和移码突变已被报道可导致 Schaaf-Yang 综合征（SYS），这是一种遗传疾病，表现为发育迟缓/智力残疾、低张力、喂养困难和自闭症谱系障碍。普拉德-威利综合征（PWS）是一种遗传疾病，其特征为严重婴儿期低张力、促性腺激素低下性性腺功能减退、儿童早期肥胖/贪食、发育迟缓/智力残疾和身材矮小。脊柱侧凸和生长激素不足在 PWS 中也很常见。有大量关于 PWS 的内分泌和代谢表型的文献记载，但没有关于 SYS 的记载。本研究旨在探讨 SYS 的激素、代谢和身体成分表型及其与 PWS 的潜在重叠。
我们在 9 名 SYS 患者（5 名女性/4 名男性；年龄 5-17 岁）中测量了血清胃饥饿素、葡萄糖、胰岛素样生长因子 1（IGF-1）、胰岛素样生长因子结合蛋白 3、促卵泡激素、黄体生成素、促甲状腺激素、游离 T4、尿酸和睾酮，并进行了全面的血脂分析。患者还接受了 X 射线和双能 X 射线吸收仪分析，以评估脊柱侧凸和骨密度。
6 名患者尽管体重正常/营养充足，但 IGF-1 水平较低，提示生长激素缺乏，类似于 PWS。如 PWS 患者所见，空腹胃饥饿素水平升高。X 射线显示 3 名患者的脊柱侧凸>10°，6 名患者的骨密度异常，Z 分数低于-2 SD。
这是对 SYS 的激素、代谢和身体成分表型的首次分析。我们的发现表明，PWS 和 SYS 之间存在显著但不完全重叠。
