Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy
Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy
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DOI：
10.1186/s13023-019-1249-4
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发表时间：
2019-12-02
影响因子：
3.7
通讯作者：
Saitoh, Shinji
中科院分区：
文献类型：
--
作者：
Negishi, Yutaka;Ieda, Daisuke;Saitoh, Shinji
研究背景Schaaf-Yang综合征（Schaaf-Yang syndrome，Schaaf-Yang syndrome，Schaaf-Yang syndrome）是一种新近发现的与印记相关的综合征，由位于15 q11-q13的母系印记MAGEL 2基因的截短突变引起。然而，确切的病理机制仍有待解决。我们对疑似Prader-Willi综合征（PWS）患者的MAGEL 2基因进行测序，以描述PWS的临床表现。我们检查了105例临床疑似PWS但没有特定PWS基因改变的患者。进行整个MAGEL 2基因的桑格测序和甲基化特异性限制性内切酶处理以检测来源亲本。详细回顾性评估临床表现。结果在6例患者（5.7%）中检测到MAGEL 2截短变异，包括一对同胞。受影响患者的所有截短变异都位于父系染色体上，而受影响兄弟姐妹的健康父亲从母亲那里继承了变异。MAGEL 2变异的患者与PWS有几个共同的特征，如新生儿肌张力减退、吸吮不良和肥胖;然而，也有独特的特征，包括关节弯曲和无法获得有意义的单词。此外，在6名患者中的4名中证实了发热性疾病后神经系统恶化的发作，这导致了严重的神经系统后遗症。结论：疑似PWS的婴儿可能存在关节弯曲，但一些独特的特征，如关节弯曲，可以帮助区分这两种综合征。发热性疾病后的神经功能恶化应被认为是一个重要的并发症。
Background Schaaf-Yang syndrome (SYS) is a newly recognized imprinting related syndrome, which is caused by a truncating variant in maternally imprinted MAGEL2 located in 15q11-q13. Yet, precise pathomechanism remains to be solved. We sequenced MAGEL2 in patients suspected Prader-Willi syndrome (PWS) to delineate clinical presentation of SYS. We examined 105 patients with clinically suspected PWS but without a specific PWS genetic alteration. Sanger sequencing of the entire MAGEL2 gene and methylation-specific restriction enzyme treatment to detect the parent of origin were performed. Clinical presentation was retrospectively assessed in detail. Results Truncating variants in MAGEL2 were detected in six patients (5.7%), including a pair of siblings. All truncating variants in affected patients were on the paternally derived chromosome, while the healthy father of the affected siblings inherited the variant from his mother. Patients with MAGEL2 variants shared several features with PWS, such as neonatal hypotonia, poor suck, and obesity; however, there were also unique features, including arthrogryposis and a failure to acquire meaningful words. Additionally, an episode of neurological deterioration following febrile illness was confirmed in four of the six patients, which caused severe neurological sequalae. Conclusions SYS can be present in infants suspected with PWS but some unique features, such as arthrogryposis, can help discriminate between the two syndromes. An episode of neurological deterioration following febrile illness should be recognized as an important complication.