Phelan-McDermid综合征42例病例系列报告  

42 cases of Phelan McDermid syndrome:A case series report

作　　者：刘春雪 邓晶鑫 王怡 李慧萍 张凯峰 董萍 徐琼 张颖 周秉睿 胡纯纯 徐秀 LIU Chunxue;DENG Jingxin;WANG Yi;LI Huiping;ZHANG Kaifeng;DONG Ping;XU Qiong;ZHANG Ying;ZHOU Bingrui;HU Chunchun;XU Xiu(Department of Child Health Care,Children's Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]国家儿童医学中心复旦大学附属儿科医院儿童保健科,上海201102

出　　处：《中国循证儿科杂志》2023年第5期388-392,共5页Chinese Journal of Evidence Based Pediatrics

基　　金：国家自然科学基金青年项目:82101945;国家自然科学基金面上项目:82171540。

摘　　要：背景Phelan-McDermid综合征(PMS)是一种罕见的神经发育障碍性疾病,SHANK3基因缺陷已被确定为PMS神经学特征的关键候选基因,PMS目前尚无临床诊断标准,确诊依赖遗传学检测。目的 总结PMS的临床表型及遗传学特征,探索PMS临床诊断路径。设计病例系列报告。方法 纳入2014年1月至2022年12月复旦大学附属儿科医院儿童保健科收治的PMS患儿,对其基因型特点、发育特征、临床症状、头颅影像、脑电图等结果进行回顾性分析,并检索文献,总结PMS临床诊断线索。主要结局指标基因型和临床表型。结果 42例PMS患儿纳入分析,男24例,女18例,平均初诊年龄3.8(1.5~12.9)岁。42例PMS患儿中,最常见的临床特征(>50%):均表现为全面发育迟缓/智力低下、语言发育障碍和注意力不集中,孤独症谱系障碍占86%、多动占82%、大运动发育延迟占52%,此外表现为颜面部畸形(耳朵大却形成不良、脸颊饱满、鼻孔前倾朝上、眼睑饱满、面中部平坦、肉质手/肉质脚、球状鼻、宽额头或额头突出)。新表型包括眉尾稀疏/缺如、体毛过重、耳廓畸形、垂眼眼型和韧带松弛。遗传学检测均发现致病变异,其中21例为包含SHANK3基因在内的22q13.3缺失(0.1~7.7 Mb,平均3.1 Mb),4例为仅有SHANK3基因部分外显子缺失,17例是SHANK3基因杂合性点突变,其中移码突变12例,无义突变5例。结论 当患儿有新生儿期肌张力低下表现,18月龄存在明显的运动和语言发育里程碑的延迟,任何年龄段、任何形式的发育评估提示至少五个能区的发育严重落后,以及存在与头长不相称的大耳和与身材不相称的肉质手/脚时,应高度怀疑PMS,需进一步完善遗传学检查来明确诊断。Background Phelan McDermid syndrome(PMS)is a rare neurodevelopmental disorder,and the SHANK3 gene defect has been identified as a key candidate gene for the neurological characteristics of this syndrome.Currently,no clinical diagnostic criteria have been established,and the confirmed diagnosis relies on genetic testing.Objective To summarize the clinical phenotype and genetic characteristics of PMS and to explore the clinical diagnostic pathway of PMS.Design Case series report.Methods Patients diagnosed with PMS who were admitted to the Department of Child Health Care at Children's Hospital of Fudan University from January 2014 to December 2022 were included.The genotype characteristics,developmental characteristics,clinical symptoms,cranial imaging,EEG and other results were retrospectively analyzed.Literature was searched to summarize clinical diagnostic clues for PMS.Main outcome measures Genotype and clinical phenotype.Results A total of 42 patients were included in the analysis,including 24 males and 18 females with an average age of 3.8(1.5-12.9)years at the first diagnosis.In this study,the most common clinical features(>50%)were global developmental delay or intellectual disability(100%),absent or severely delayed speech(100%),inattention(100%),ASD(86%),hyperactivity(82%),delayed major motor development milestones(52%).Other were facial deformities including large but poorly formed ears,full or puffy cheeks,anteverted nares,periorbital fullness,flat midface,fleshy hands/feet,bulbous nose,wide forehead or protruding forehead.The new phenotypes included sparse or absent eyebrow tail,excessive body hair,auricular deformities,drooping eye type,and ligament relaxation.Genetic testing revealed that all 42 cases were pathogenic mutations,of which 21 were 22q13.3 deletions(0.1-7.7Mb,average 3.1Mb)including the SHANK3 gene,4 were only partial exon deletions of the SHANK3 gene,and 17 were heterozygous point mutations in the SHANK3 gene,including 12 frameshift mutations and 5 nonsense mutations.Conclusions When ther

关 键 词：Phelan-McDermid综合征 22q13.3缺失综合征 SHANK3基因 全面发育迟缓 语言发育障碍 

分 类 号：R741[医药卫生—神经病学与精神病学]