Godler David E, Singh Deepan, Butler Merlin G
Diagnosis and Development, Murdoch Children's Research Institute, Royal Children's Hospital.
Faculty of Medicine, Dentistry and Health Sciences, Department of Paediatrics, University of Melbourne, Parkville.
Curr Opin Psychiatry. 2025 Mar 1;38(2):95-100. doi: 10.1097/YCO.0000000000000981. Epub 2024 Dec 18.
Prader-Willi (PWS) and Angelman (AS) syndromes arise from errors in 15q11-q13 imprinting. This review describes recent advances in genomics and how these expand our understanding of these rare disorders, guiding treatment strategies to improve patient outcomes.
PWS features include severe infantile hypotonia, failure to thrive, hypogonadism, developmental delay, behavioral and psychiatric features, hyperphagia, and morbid obesity, if unmanaged. AS presents severe intellectual disability, motor dysfunction, seizures, absent speech, and a characteristic happy demeanor. Standard-of-care testing involves SNRPN promoter methylation, microarray and genomic analyses for individuals presenting with these features. These tests identify syndromic-specific DNA methylation patterns and molecular genetic classes responsible for disease etiology. This review provides an update on studies of genotype-phenotype relationships and novel genomic technologies used for diagnostic purposes.
We give an overview and update on the genetics and underlying mechanisms associated with symptoms and potential treatments with focus on features reported to be different between specific molecular genetic classes. The review also describes laboratory testing methods for diagnosis of these imprinting disorders with implications for clinical practice.
普拉德-威利综合征（PWS）和安吉尔曼综合征（AS）是由15q11-q13印记错误引起的。本综述描述了基因组学的最新进展，以及这些进展如何扩展我们对这些罕见疾病的理解，指导治疗策略以改善患者预后。
PWS的特征包括严重的婴儿期肌张力减退、生长发育迟缓、性腺功能减退、发育迟缓、行为和精神特征、食欲亢进，如果不加以控制还会导致病态肥胖。AS表现为严重智力残疾、运动功能障碍、癫痫发作、失语以及特有的愉快面容。标准的护理检测包括对出现这些特征的个体进行SNRPN启动子甲基化、微阵列和基因组分析。这些检测可识别与疾病病因相关的综合征特异性DNA甲基化模式和分子遗传类别。本综述提供了关于基因型-表型关系研究以及用于诊断目的的新型基因组技术的最新信息。
我们概述并更新了与症状和潜在治疗相关的遗传学及潜在机制，重点关注特定分子遗传类别之间报道存在差异的特征。本综述还描述了这些印记障碍的实验室诊断方法及其对临床实践的影响。
