5p15.1-5p15.33重复1例并文献复习

A case of 5p15.1-5p15.33 duplication and literature review

目的分析5号染色体短臂(5p)末端的5p15.1-5p15.33重复患儿的临床特点及遗传学特征。方法收集四川大学华西第二医院儿童重症医学科于2021年7月确诊的存在5p15.1-5p15.33重复的1例患儿,总结其临床资料,并对文献报道的5p重复综合征的病例特点进行总结分析。结果患儿为男性,就诊时1岁5个月,以出生后逐渐出现生长受限及发育迟缓为主要临床表现,伴颅面畸形;7月龄时因四肢抽动被诊断为癫痫;目前为2岁龄,仍反复抽搐,不能抬头、独坐,不会爬,不会咿呀说话,伴肌张力减退。反复行头颅磁共振成像检查均示胼胝体发育不良。患儿父母表型正常。患儿拷贝数变异测序结果显示染色体5p15.1-5p15.33(chr5:1934522-18905656)存在部分重叠,根据拷贝数变异评判标准,判定为致病拷贝数变异,父母未检出异常。根据本研究设定的检索策略,共检索到10篇相关文献(均为英文)报道的17例及数据库中收录的4例,加上本例,共22例5p重复综合征患者,其中17例年龄≤14岁,起病年龄7(0,18)岁,男女比约为1.1∶1。22例患者中颅面畸形19例,发育障碍18例,骨骼/肌肉发育异常15例,自闭症11例,注意力缺陷多动障碍9例,智力障碍8例,肥胖症5例,癫痫5例,先天性心脏发育异常2例,肌张力减退4例,斜视/远视2例,表现为胼胝体发育不良、内分泌功能紊乱、腹股沟疝、脐疝各1例;多发畸形19例,单一畸形3例。结论5p15.1-5p15.33重复可能为该患儿的遗传学病因。面部畸形、发育迟缓、骨骼/肌肉发育异常、智力残疾、自闭症谱系障碍、注意力缺陷多动障碍是5p拷贝数重复最主要的临床表型;胼胝体发育不良可能为该位置染色体重复的扩展表型。

Objective To analyze the clinical and genetic features of the children with 5p15.1-5p15.33 duplication at the end of the short arm of chromosome 5(5p).Methods Clinical data of a 5p15.1-5p15.33 duplicative patient diagnosed in the Department of Pediatric Intensive Care Unit of West China Second University Hospital of Sichuan University in July 2021 were collected,and the characteristics of the patients of 5p duplication syndrome reported in the literatures were summarized and analyzed.Results The boy was 1 year and 5 months old at the time of admission.The main clinical manifestations included growth restriction and developmental delay after birth,accompanied by craniofacial deformities.At 7 months old,he was diagnosed as epilepsy due to convulsive limbs.At present,he is 2 years old,still has recurrent convulsions,can not raise his head,sit alone,crawl and talk,with hypotonia.Repeated cranial magnetic resonance imaging showed agenesis of the corpus callosum.The child′s parents had normal phenotypes.His copy number variation sequencing results showed partial overlap of chromosome 5p15.1-5p15.33(chr5:1934522-18905656),which was determined as pathogenic copy number variation according to copy number variations evaluation criteria,and no abnormality was detected in his parents.According to the retrieval strategy set in this study,10 literatures(all in English,reporting 17 cases)were retrieved,and a total of 225p duplication syndrome patients(including this case and 4 cases included in databases)were included.Seventeen of the 22 patients were younger than 14 years old with a onset age of 7(0,18)years,and the male to female ratio was about 1.1∶1.Among the 22 patients,craniofacial malformation was found in 19 patients,developmental disorder in 18,bone/muscle dysplasia in 15,autism in 11,attention deficit hyperactivity disorder in 9,mental retardation in 8,obesity in 5,epilepsy in 5,congenital heart dysplasia in 2,hypotonia in 4,strabismus/hyperopia in 2,and corpus callosum dysplasia,endocrine dysfunction,inguinal hernia as well as umbilical hernia in 1,respectively.There were 19 cases of multiple malformation and 3 cases of single malformation.Conclusions 5p15.1-5p15.33 duplication may be the genetic cause of this child.Facial malformation,developmental delay,skeletal/muscular dysplasia,intellectual disability,autism spectrum disorder and attention deficit hyperactivity disorder are the main clinical phenotypes of 5p copy number duplication.Corpus callosum dysplasia may be an extended phenotype of chromosome duplication at this location.