KMT2A基因变异所致Wiedemann-Steiner综合征患儿3例的临床特征及遗传学分析

Clinical features and genetic analysis of three cases of Wiedemann-Steiner syndrome with KMT2A gene variants

目的探讨3例Wiedemann-Steiner综合征(Wiedemann-Steiner syndrome,WSS)患儿的临床特征及遗传学病因,提高对该病的认识。方法回顾性分析2016年8月至2022年7月郑州大学附属儿童医院内分泌遗传代谢科就诊的3例WSS患儿的一般资料、临床特点、生长激素激发试验等实验室检测、垂体磁共振等影像学检查结果,予以重组人生长激素(recombinant human growth hormone,rhGH)治疗,对先证者及家系进行遗传学检测。结果3例WSS患儿中男2例、女1例,4.8~11.3岁,均因身材矮小就诊,伴智力落后、特殊面容、多毛;病例3生长激素激发试验结果提显示生长激素缺乏,且伴骨龄明显落后;3例患儿垂体磁共振均正常,均予rhGH治疗1~5年,身高分别增加0.9 SD、1 SD、2.2 SD,其中病例3随访至终身高为157.9 cm。基因检测结果示KMT2A基因杂合变异,分别为chr11:118353970-118356519区域存在2.5 Kb片段的杂合缺失、c.11081delp.K3694Sfs*3、c.5803-3T>G,3例基因变异均为未报道过的新变异,最终诊断WSS。结论对表现为生长发育迟缓、智力落后、特殊面容、多毛症等患儿需考虑WSS,上述发现拓宽了KMT2A基因的变异谱和临床表型谱。

Objective To explore the clinical characteristics and genetic etiology of 3 children with Wiedemann-Steiner syndrome(WSS)and to improve the understanding of the disease.Methods A retrospective analysis was conducted on the general data,clinical characteristics,laboratory tests such as growth hormone stimulation test,and imaging examinations such as pituitary magnetic resonance imaging of three children with WSS who visited Chidren's Hospital Affiliated to Zhengzhou University from August 2016 to July 2022.Recombinant human growth hormone(rhGH)treatment was performed,and genetic testing was conducted on the proband and family.Results Among the 3 patients,2 were males and 1 was female,aged 4.8 to 11.3 years.All patients were diagnosed with short stature,accompanied by intellectual disability,special facial features,and hirsutism.Growth hormone stimulation test results showed that the case 3 had growth hormone deficiency with significantly delayed bone age.All case showed normal pituitary magnetic resonance imaging,then received rhGH treatment for 1 to 5 years.The height increased by 0.9 SD,1 SD,and 2.2 SD,respectively,with case 3 followed up to a lifetime height of 157.9 cm.Genetic testing results showed heterozygous mutations in the KMT2A gene.The results showed heterozygous deletions of 2.5 Kb fragments in the chr11:118353970-118356519 region,c.11081delp.K3694Sfs*3,and c.5803-3T>G.All three gene mutations were newly reported.The final diagnoses were WSS.Conclusion For children with delayed growth and development,intellectual disability,special facial features and hirsutism,WSS should be considered.This study broadens the variant spectrum and clinical phenotypic spectrum of the KMT2A gene.