先天性肌张力低下新生儿32例的遗传学分析

Genetic analysis of 32 newborns with congenital hypotonia

目的探讨先天性肌张力低下新生儿的致病性基因突变特点、临床特征以及预后情况,为临床医生早期识别疾病及选择合理的干预措施提供参考。方法回顾性分析安徽省儿童医院新生儿重症监护病房2019年6月至2022年6月收治的以肌张力低下为主要临床表现的新生儿的临床特征及基因检测结果。结果研究共纳入32例患儿,均有肌张力低下表现,其中中枢性肌张力低下20例(62.5%),周围性肌张力低下12例(37.5%)。经基因测序后共发现21种疾病,26种基因型,其中新发突变来源的基因型有14种(RIT1、KRAS、BRAF、PHOX2B、HNRNPK、RAI1、KMT2D、OTC、AHDC1、DMD、COL12A1、MT-ATP6、FLNC、RYR1)。对所有患儿进行随访,死亡20例。结论先天性肌张力低下病因复杂,基因测序可以提高早期诊断率,扩宽先天性肌张力低下的表型-基因型谱,替代部分侵入性检查,同时指导临床管理以及家庭的遗传咨询。

Objective To explore the characteristics,clinical features and prognosis of pathogenic gene mutation of newborns with congenital hypotonia,and provide a reference for clinicians to early identify diseases and choose reasonable treatment schemes.Methods The clinical characteristics and gene test results of newborns with hypotonia as the main clinical manifestation in the NICU of Anhui Children′s Hospital from June 2019 to June 2022 were retrospectively analyzed.Results A total of 32 children with hypotonia diagnosed by gene tests were included.Among the 32 cases,20 cases(62.5%)had central hypotonia and 12 cases(37.5%)had peripheral hypotonia.A total of 21 diseases and 26 genotypes were detected,including 14 new mutations(RIT1,KRAS,BRAF,PHOX2B,HNRNPK,RAI1,KMT2D,OTC,AHDC1,DMD,COL12A1,MT-ATP6,FLNC,RYR1).All patients were followed up,and 20 patients died.Conclusion The etiology of congenital hypotonia is complex.Gene sequencing can improve the early diagnosis rate,broaden the phenotype-genotype spectrum of congenital hypotonia,so it can be used to replace some invasive tests,and guide clinical management and genetic counselling for families.