1例RAF1基因变异导致的Noonan综合征5型

A Case of Noonan Syndrome Type 5 Caused by RAF1 Gene Mutation

目的通过分析1例RAF1基因变异导致的Noonan综合征5型的临床及分子遗传学特点,提高对该疾病的认识。方法回顾分析2016年2月在郑州大学附属儿童医院诊断的RAF1基因变异患儿的病例资料,总结RAF1基因变异致Noonan综合征5型的临床表型及分子遗传学特征。结果初诊时3岁患儿身材矮小,同时有前额长,双耳耳位低,耳垂大,后发迹低,颈蹼,通贯掌,手纹粗等特殊体征,生长激素激发试验提示生长激素部分缺乏,心脏彩超未见明显异常,建议完善基因检测,未做。7岁时因身材严重矮小给予生长激素改善身高增长,定期复查相关指标及心脏彩超、心电图预防心脏并发症。患儿应用生长激素治疗2年半,身高增长19.2cm,9岁半时复查心脏彩超提示心室肌增厚、室壁运动幅度略增强、左房大、左室腔略小,二、三尖瓣腱索冗长,瓣叶略脱垂,二、三尖瓣反流(轻度),停用生长激素治疗。完善全外显子基因检测提示RAF1基因p.R256G致病性变异,临床和基因均明确为Noonan综合征5型。结论对于存在特殊面容的矮小症,应及时完善基因检测,及早明确诊断,避免误诊及延时治疗。

Objective To analyze the clinical and molecular genetic characteristics of a case of Noonan syndrome type 5 caused by RAF1 gene variation,so as to improve the understanding of this disease.Methods The clinical data of children with RAF1 gene mutation diagnosed in Children's Hospital Affiliated to Zhengzhou University in February 2016 were retrospectively analyzed,and the clinical phenotype and molecular genetic characteristics of Noonan syndrome type 5 caused by RAF1 gene mutation were summarized.Results At the time of initial diagnosis,the 3-year-old child was short in stature and had special signs such as long forehead,low ears,large earlobes,low posterior hair,cervical webbed,penetration palm,coarse hand lines,etc.The growth hormone stimulation test suggested that the growth hormone was partially deficient,and the cardiac color ultrasound showed no obvious abnormalities.When she was 7 years old,she was given growth hormone to improve her height growth because of severe short stature.She was reexamined regularly for related indicators,color Doppler ultrasound and electrocardiogram to prevent cardiac complications.The child was treated with growth hormone for 2 and a half years,and his height increased by 19.2cm.When he was 9 and a half years old,color echocardiography showed thickening of ventricular muscle,slightly enhanced amplitude of wall motion,large left atrium,slightly smaller left ventricular lumen,long chorda tendineae of the second and tricuspid valve,slight valve prolapse,regurgitation of the second and tricuspid valve(mild).Complete whole-exon genetic testing suggested a p.R256G pathogenic variant of RAF1 gene,which was clinically and genetically identified as Noonan syndrome type 5.Conclusion For short stature with special facial features,genetic testing should be improved in time,early diagnosis should be made,and misdiagnosis and delayed treatment should be avoided.