【摘要】 目的 总结1例罕见的22号染色体长臂末端缺失导致的Phelan-McDermid综合征(PMS)患儿的临床表现、影像、实验室检测及基因分析结果，并通过文献复习为疾病诊断、遗传咨询提供参考依据。方法 回顾性分析2021年11月在暨南大学附属第一医院儿科明确诊断的1例PMS患儿的临床资料及家系全基因组测序资料。查阅文献总结PMS患儿的临床特点及基因变异特点。结果 该患儿临床主要症状为肌张力低下、全面性发育迟缓、语言障碍、孤独症谱系障碍、轻微面部畸形、手足肥大、趾甲发育不良、骶骨酒窝，头颅MRI提示脑白质髓鞘化延迟；全基因组高通量测序结果显示拷贝数变异异常，确认染色体chr22:46 519 480-51 304 566上存在4.79 Mb的新发缺失突变并涉及SHANK3缺失。文献复习发现，PMS患者常见的发育及行为特征为语言缺乏或严重落后(100.00%)、发育迟缓/智力障碍(91.89%)、肌张力减退(73.17%);轻微畸形特征主要表现为大耳(21.88%)、睑裂狭小(21.88%)、斜视(18.75%)。遗传学分析：12例患儿仅是SHANK3点突变或缺失，29例患儿包含SHANK3以上的片段缺失。其中，点突变的患儿基因变异类型有2种，8例是移码突变(89.00%),1例为无义突变(11.00%)。遗传方式：新发突变(100.00%)。结论 PMS的主要表型为肌张力低下、全面性发育迟缓、严重语言障碍、轻微畸形和孤独症谱系障碍等。22号染色体长臂末端缺失、突变涉及SHANK3缺失是其致病原因。基因型与表型关联分析表明，缺失的片段大小与临床表现多样性和/或严重程度呈正相关，此外，缺失片段中其他基因缺失也参与了PMS的病因学。更多还原

【Abstract】 Objective To summarize the clinical manifestations, imaging, laboratory tests and gene analysis results of a rare case of Phelan-McDermid syndrome( PMS) caused by long arm deletion of chromosome 22, and provide reference for disease diagnosis and genetic counseling through literature review.Methods The clinical data and family genome-wide sequencing data of a child with PMS diagnosed in pediatrics of the First Affiliated Hospital of Jinan University in November 2021 were retrospectively analyzed. The clinical characteristics and genetic variation of PMS children were summarized by consulting literatures.Results The main clinical symptoms of the child were low muscle tone, comprehensive development retardation, language disorder, slight facial deformity, hand and foot hypertrophy, dysplasia of toenail, sacrum dimple and autism spectrum disorder. Brain MRI showed delayed white matter myelination. The whole genome sequencing showed that there was a denovo abnormal copy number variation of 4.79 Mb deletion on chromosome chr22:46 519 480-51 304 566 involving the SHANK3 deletion. Literature review showed that the most common developmental and behavioral characteristics of PMS patients were speech delay(100.00%), developmental disability/intellectual disability(91.89%) and hyperactivity(73.17%). Dysmorphic features were mainly abnormal ear or big ear(21.88%) descending palpebral fissure(21.88%), and strabismus(18.75%). Genetic analysis showed that 12 cases of children with SHANK3 mutation or deletion, 29 cases of children with SHANK3 or more fragment deletion. Among them, there were two types of gene mutation in children with point mutation, 8 cases were frameshift mutation(89.00%), and 1 case was nonsense mutation(11.00%). The genetic pattern was denovo mutations(100.00%).Conclusion The main phenotypes of Phelan-McDermid syndrome are low muscle tone, comprehensive developmental retardation, severe language disorder, slight deformity and autism spectrum disorder. The deletion of the long arm end of chromosome 22 and the mutation involving SHANK3 deletion are the pathogenic reasons. Genotype-phenotype correlation analysis showe that the size of deletion is positively correlated with the diversity and/or severity of clinical manifestations. In addition, other deletion fragments are also involved in the etiology of PMS.更多还原