核苷酸切除修复障碍16例临床特征及文献复习

Clinical characteristics of 16 patients with nucleotide excision repair disorders and literature review

目的总结核苷酸切除修复(NER)障碍患儿的临床特征及基因突变位点。方法回顾性分析2008年10月至2022年2月中国人民解放军总医院收治住院及2015年10月至2022年2月首都医科大学附属北京儿童医院门诊收治确诊的NER障碍患儿的临床资料,并对国内外已报道的中国病例进行文献复习。结果1.在16例NER障碍患儿中男6例,女10例;起病年龄为7.5(4.0,12.0)个月;确诊年龄为42.0(21.5,77.0)个月;包括3种类型:科凯恩综合征(CS)13例、着色性干皮病(XP)2例、眼-脑-面-骨综合征(COFS)1例;涉及4个致病基因,11例CSA、3例CSB、1例XPG、1例XPD。16例患儿以光过敏及发育落后起病,各型均有神经系统症状,XP及CS患儿均有皮肤症状。CS患儿有特殊面容、视听障碍、小头畸形、神经影像学特征改变。COFS伴宫内发育迟缓。2.文献复习结果:共检索到既往报道中国病例96例,共涉及6种类型,其中45例CS,44例XP,毛发低硫营养不良4例,COFS、XP-CS、紫外线敏感综合征各1例。涉及9种突变基因,33例CSA、15例XPA、13例CSB、10例XPV、9例XPC、7例XPG、7例XPD、1例XPF、1例MPLKIP。常见症状为生长发育障碍(62例)、皮肤光过敏(61例)、特殊面容(52例)、智力障碍(49例)、小头畸形(48例)等。33/36例(91.7%)影像学示基底核或苍白球钙化。3例在孕期有宫内发育迟缓、小头畸形等表现。结论妊娠期出现宫内发育迟缓、小头畸形及临床发现皮肤光过敏、特殊面容、生长发育落后、智力障碍、肌张力高、基底核钙化等异常者,应考虑NER相关疾病可能,应早期行相关基因检测进一步明确诊断。

Objective To summarize the clinical manifestations and gene mutation features of patients with nucleotide excision repair(NER)disorders.Methods A retrospective analysis was made on clinical data of patients with NER disorders who were admitted to the Chinese People′s Liberation Army General Hospital from October 2008 to February 2022 and diagnosed in the Outpatient Department of Beijing Children′s Hospital,Capital Medical University from October 2015 to February 2022.Literature on previously reported Chinese patients with NER disorders was reviewed.Results(1)A total of 16 patients with NER disorders were enrolled,including 6 males and 10 females.The onset age was 7.5(4.0,12.0)months and the age at diagnosis was 42.0(21.5,77.0)months.There were 3 types of NER disorders:Cockayne syndrome(CS)in 13 cases,Xeroderma Pigmentosum(XP)in 2 cases and Cerebro-Oculo-Facio-Skeletal syndrome(COFS)in 1 case.Four disease-causing genes were detected:CSA gene in 11 cases,CSB gene in 3 cases,XPG gene in 1 case,and XPD gene in 1 case.The first symptoms of the 16 patients were photosensitivity and developmental delay,and neurological symptoms were observed in all the 3 NER disorder types.XP and CS patients had skin symptoms.CS patients presented typical facial features,visual and auditory impairment,microcephaly and changes in neuroimaging features.COFS patients showed intrauterine growth retardation.(2)Results of literature review:a total of 96 Chinese patients reported were retrieved,involving 6 disease types,including CS in 45 cases,XP in 44 cases,trichothiodystrophy in 4 cases,COFS in 1 case,XP-CS in 1 case,and ultraviolet sensitive syndrome in 1 case.Nine mutated genes were identified:CSA in 33 cases,XPA in 15 cases,CSB in 13 cases,XPV in 10 cases,XPC in 9 cases,XPG in 7 cases,XPD in 7 cases,XPF in 1 case,and MPLKIP in 1 case.The common symptoms were growth failure(62 cases),skin photosensitivity(61 cases),typical facial features(52 cases),mental retardation(49 cases)and microcephaly(48 cases).Among 36 cases had imaging data 33 cases(91.7%)had calcification of basal nucleus or globus pallidus.Three cases had intrauterine growth retardation and microcephaly during pregnancy.Conclusions Patients with such prenatal manifestations as intrauterine growth retardation and microcephaly or with typical symptoms like skin photosensitivity,typical facial features,growth failure,mental retardation,hypertonia,and calcifications of basal ganglia should be suspected of NER disorders.Early genetic testing is recommended to confirm the diagnosis.