Noonan综合征7例临床及遗传学分析

目的分析儿童Noonan综合征的临床及遗传学特征。方法收集2018年1月至12月诊断的7例Noonan综合征患儿的临床资料,通过全外显子联合Sanger测序完成家系分析和解读。结果男4例、女3例,均因身高增长缓慢就诊,诊断中位年龄3岁3个月(8个月~13岁1个月)。6例患儿具有Noonan综合征特征性面容,6例有色素沉着,以及头发卷曲、颈蹼、通贯掌、脊柱侧弯及隐睾等,6例患儿智力发育迟缓。4例患儿的生长激素激发试验峰值>10 ng/mL,类胰岛素生长因子均无异常;5例心脏结构异常,其中肺动脉瓣狭窄2例、房间隔缺损2例、二尖瓣关闭不全1例、室间隔增厚1例。7例患儿均发现PTPN11基因错义突变,6例为新生突变,1例为父源性,突变均符合ACMG致病性突变标准。结论 Noonan综合征以生长缓慢为主要表现,可有身材矮小、智力发育落后及特殊面容,高发心脏结构改变。PTPN11突变导致Noonan综合征均为错义突变,以新生突变为主。

Clinical and genetic analysis of Noonan syndrome in 7 children

Objective To explore the clinical and genetic characteristics of Noonan syndrome in children. MethodsThe clinical data of Noonan syndrome in 7 children diagnosed from January to December 2018 were collected. Familial analysis and interpretation were completed by whole exon sequencing and Sanger sequencing. Results Four boys and 3 girls visited the clinic for their short stature and the median age of diagnosis was 3 years and 3 months(8 months to 13 years and 1 month). Six children had characteristic features of Noonan syndrome, such as pigmentation, curly hair, webbed neck, palmthrough, scoliosis and cryptorchidism. Six children had mental retardation. Four children had a peak GH concentration>10 ng/mL in provocation test, and there was no abnormality of insulin-like growth factor. Abnormal cardiac structure was founded in 5 cases, including 2 cases of pulmonary stenosis, 2 cases of atrial septal defect, one case of mitral insufficiency and one case of hypertrophic ventricular septal. Missense mutations of PTPN11 gene were found in all 7 children, including 6 de novo mutations and one paternal mutation, and all these mutations were considered to be pathogenic according to the ACMG Practice Guideline. Conclusions Growth failure is the main presentation in patients with Noonan syndrome. Short stature, special facial features and mental retardation are common manifestations. Many cardiovascular phenotypes occur in Noonan syndrome. Noonan syndrome is caused by missense mutations in PTPN11, mainly de novo mutation.