3M综合征患儿4例的临床特点及文献复习

Clinical characteristics of four children with 3M syndrome and a literature review

目的分析3M综合征的临床特征及用生长激素治疗的效果。方法回顾性分析2014年1月至2022年2月在湖南省儿童医院经全外显子组测序确诊的3M综合征患儿的临床表现、基因测序结果及生长激素治疗情况,并系统回顾相关文献。结果4例患儿均存在严重的生长落后、特殊面容和骨骼异常。基因检测提示2例患儿存在CUL7基因纯合变异,分别为c.4717C>T(p.R1573*)和c.967_993delins CAGCTGG(p.S323Qfs*33),2例患儿携带OBSL1基因杂合变异,分别为c.1118G>A(p.W373*)、c.458dupG(p.L154Pfs*1002)和c.690dupC(p.E231Rfs*23),其中c.967_993delinsCAGCTGG和c.1118G>A既往未见报道。文献复习共纳入18例中国3M综合征患儿,其中CUL7基因变异者11例(11/18,61.1%),OBSL1基因变异者7例(7/18,38.9%),未发现CDCC8基因变异者。患儿的男女比例为1∶1,主要临床表现与文献报道一致。4例患者接受了生长激素治疗,其中3人治疗后有明显生长加速,均未发生不良反应。结论3M综合征具有典型的外貌特征,同时伴有显著的身材矮小。临床对于身高在-3s以下且伴有特殊面容的儿童应进行基因检测。生长激素治疗对3M综合征患者的远期有效性尚待进一步的观察。

Objective To analyze the clinical features of 3M syndrome and effect of growth hormone therapy.Methods Clinical data of four children diagnosed with 3M syndrome by whole exome sequencing at Hunan Children′s Hospital from January 2014 to February 2022 were retrospectively analyzed,which included clinical manifestation,results of genetic testing and recombinant human growth hormone(rhGH)therapy.A literature review was also carried our for Chinese patients with 3M syndrome.Results The clinical manifestations of the 4 patients included severe growth retardation,facial dysmorphism and skeletal malformations.Two patients were found to harbor homozygous variants of CUL7 gene,namely c.4717C>T(p.R1573*)and c.967_993delinsCAGCTGG(p.S323Qfs*33).Two patients were found to harbor 3 heterozygous variants of the OBSL1 gene including c.1118G>A(p.W373*),c.458dupG(p.L154Pfs*1002)and c.690dupC(p.E231Rfs*23),among which c.967_993delinsCAGCTGG and c.1118G>A were unreported previously.Eighteen Chinese patients with 3M syndrome were identified through the literature review,including 11 cases(11/18,61.1%)carrying CUL7 gene variants and 7 cases(7/18,38.9%)carrying OBSL1 gene variants.The main clinical manifestations were in keeping with previously reported.Four patients were treated with growth hormone,3 showed obvious growth acceleration,and no adverse reaction was noted.Conclusion 3M syndrome has a typical appearance and obvious short stature.To attain accurate diagnosis,genetic testing should be recommended for children with a stature of less than-3s and facial dysmorphism.The long-term efficacy of growth hormone therapy for patients with 3M syndrome remains to be observed.