Huang Zhongwen, Lu Wei, Zhang Ping, Lu Yulan, Chen Liping, Kang Wenqing, Yang Lin, Li Gang, Zhu Jitao, Wu Bingbing, Zhou Wenhao, Wang Huijun
Center for Molecular Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Department of Endocrinology and Inherited Metabolic Diseases1, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Ann Transl Med. 2023 Jun 30;11(9):312. doi: 10.21037/atm-22-4396. Epub 2023 May 31.
Schaaf-Yang syndrome (SYS) is a recently identified rare neurodevelopmental disorder characterized by neonatal hypotonia, feeding difficulty, joint contractures, autism spectrum disorder and development delay/intellectual disability. It is mainly caused by truncating variants in maternally imprinted gene within the Prader-Willi syndrome critical region 15q11-q13. Clinical diagnosis of SYS is difficult for clinicians due to its rarity and highly variable phenotypes, while unique inheritance patterns also complicate genetic diagnosis. To date, no published papers have analyzed the clinical consequences and molecular changes in Chinese patients.
In this study, we retrospectively investigated the mutation spectrums and phenotypic features of 12 SYS infants. The data were from a cohort of critically ill infants from the China neonatal genomes project (CNGP), sponsored by Children's Hospital of Fudan University. We also reviewed relevant literature.
Six previously reported mutations and six novel pathogenic variations of were identified in 12 unrelated infants. Neonatal respiratory problems were the major complaint for hospitalization, which occurred in 91.7% (11/12) cases. All babies displayed feeding difficulties and a poor suck postnatally, and neonatal dystonia was present in 11 of the cases; joint contractures and multiple congenital defects were also observed. Interestingly, we found that 42.5% (57/134) of the reported SYS patients, including ours carried variants in the c.1996 site, particularly the c.1996dupC variant. The mortality rate was 17.2% (23/134), with the median age of death between 24 gestational weeks in fetuses and 1-month-old in infants. Respiratory failure was the leading cause of death in live-born patients (58.8%, 10/17), especially during the neonatal period.
Our findings expanded the genotype and phenotype spectrum of neonatal SYS patients. The results demonstrated that respiratory dysfunction was a typical characteristic among Chinese SYS neonates that should attract physicians' attention. The early identification of such disorders allows early intervention and can further provide genetic counseling as well as reproductive options for the affected families.
Schaaf-Yang综合征（SYS）是一种最近发现的罕见神经发育障碍，其特征为新生儿肌张力减退、喂养困难、关节挛缩、自闭症谱系障碍以及发育迟缓/智力残疾。它主要由普拉德-威利综合征关键区域15q11-q13内母系印记基因的截短变异引起。由于SYS罕见且表型高度可变，临床医生对其进行临床诊断存在困难，而独特的遗传模式也使基因诊断变得复杂。迄今为止，尚无已发表的论文分析中国患者的临床后果和分子变化。
在本研究中，我们回顾性调查了12例SYS婴儿的突变谱和表型特征。数据来自由复旦大学附属儿科医院发起的中国新生儿基因组计划（CNGP）中的一组危重症婴儿。我们还查阅了相关文献。
在12例无亲缘关系的婴儿中鉴定出6种先前报道的突变和6种新的致病变异。新生儿呼吸问题是住院的主要原因，发生在91.7%（11/12）的病例中。所有婴儿出生后均表现出喂养困难和吸吮无力，11例出现新生儿肌张力障碍；还观察到关节挛缩和多种先天性缺陷。有趣的是，我们发现包括我们的患者在内，42.5%（57/134）的已报道SYS患者在c.1996位点携带变异，特别是c.1996dupC变异。死亡率为17.2%（23/134），死亡中位年龄在胎儿24孕周至婴儿1月龄之间。呼吸衰竭是活产患者的主要死亡原因（58.8%，10/17），尤其是在新生儿期。
我们的研究结果扩展了新生儿SYS患者的基因型和表型谱。结果表明，呼吸功能障碍是中国SYS新生儿的典型特征，应引起医生的注意。早期识别此类疾病可进行早期干预，并能进一步为受影响家庭提供遗传咨询和生育选择。
