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中国循证儿科杂志

中国循证儿科杂志 ›› 2018, Vol. 13 ›› Issue (6): 452-458.

• 论著 • 上一篇    下一篇

ANKRD11基因突变所致KBG综合征1例并文献复习

李秋月，杨琳，吴静，陆炜，章淼滢，罗飞宏   

  1. 复旦大学附属儿科医院内分泌代谢科 上海，201102
  • 收稿日期:2018-12-15 修回日期:2018-12-24 出版日期:2018-12-25 发布日期:2018-12-25
  • 通讯作者: 罗飞宏

A case of KBG syndrome caused by mutation of ANKRD11 gene and literature review

LI Qiu-yue, YANG Lin, WU Jing, LU Wei, ZHANG Miao-ying, LUO Fei-hong   

  1. Endocrinology and Metabolism, Children's Hospital of Fudan University, Shanghai, 201102, China
  • Received:2018-12-15 Revised:2018-12-24 Online:2018-12-25 Published:2018-12-25
  • Contact: LUO Fei-hong

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摘要： 目的报告1例KBG综合征患儿的临床表型和基因型特点，提高对本病的认识。方法采集1例KBG综合征患儿的临床资料，采集家系外周血行全外显子基因测序（WES），Sanger测序验证。检索中英文数据库中已报道的ANKRD11突变导致KBG综合征的病例，总结临床特征及基因突变谱。结果女，8 岁，因“生长发育迟缓”就诊。生后匀称性矮小并有特殊面容，手短伴第5手指弯曲，语言发育迟缓；生长激素激发峰值5.7 ng·mL-1；WES检测发现ANKRD11基因c.6792dupC（p.P2271Pfs*8）杂合突变，导致ANKRD11蛋白自第2 271位起后第8位编码天冬氨酸的密码子突变为终止密码子，使高度保守的羧基末端肽链合成提前终止，为有害突变。文献复习共检索到22篇（加上本文病例共155例KBG综合征患者），男∶女比1.5∶1，包括ANKRD11基因突变114例和16q24.3微缺失型41例，临床表现以颅面部异常如三角形脸（31.8%~64.2%）、眼距过宽（24.0%~61.7%）、鼻梁宽（31.3%~82.7%）、人中异常（52.4%~86.8%）、中枢神经系统异常如语言发育迟缓（92.6%~93.6%）、智力低下（66.7%~73.0%）、学习障碍（71.4%~75.0%），上颌中切牙过大（55.6%~844%）、骨骼异常如小指侧弯（53.5%~72.6%）和矮小（57.5%~72.6%）最为经典。ANKRD11突变型及16q24.3微缺失型分别检出先天性心脏病12.2%， 28.9%；16q24.3微缺失型检出特发性血小板减少性紫癜（ITP）12.2%。结论语言发育迟缓、学习障碍、智力低下等中枢神经系统异常表现是KBG综合征特异性表型，如合并典型的颅面部异常（三角形脸、眼距过宽、鼻梁宽、人中异常）、上颌中切牙过大、矮小及小指侧弯，需考虑ANKRD11基因突变型；16q24.3微缺失型除表现中枢神经系统特异性表型外，常合并隐睾、先天性心脏病及ITP等异常。

Abstract: ObjectiveTo summarize the case of KBG syndrome (macrodontia, mental retardation, characteristic facies, short stature, and skeletal anomalies，KBGS), analyze ANKRD11 gene sequencing results in China, and review the literature to improve the understanding of the disease. MethodsThe clinical data of a patient with KBGS were collected. Whole Exon Sequencing of peripheral blood in the family was done and verified by Sanger method. ANKRD11 mutations from PubMed，Wanfang Database and China National Knowledge Infrastructure up to November 1st, 2018 were searched. The related features along with the clinical and gene mutation spectrums of KBGS cases and 16q24.3 microdeletion cases were summarized. ResultsThe patient, female, 8 years old, presented with "growth retardation". The patient was proportioned short stature with special craniofacial features after birth, and she also presented with short fingers combined with bending, wide gait based, exercise, and language development retardation. ANKRD11 gene was found with c.6792dupC (p. P2271Pfs*8) heterozygous mutation, leading to premature termination of a highly conserved carboxyl terminal protein. A total of 22 articles were retrieved from the literature review, and a total of 155 patients with KBGS including the case reported in this article were analyzed. Among them, 114 patients were with ANKRD11 mutation and 41 patients with 16q24.3 microdeletion. The ratio of male to female in KBGS patients was about 1.5. The clinical manifestations were cranial facial abnormalities, language development delay, mental retardation, learning disability, micrognathia, short finger combined with fifth finger bending, short stature. Congenital heart diseases were detected in the type of ANKRD11 mutant and 16q24.3 microdeletion for 12.2% and 28.9%, respectively. ITP was detected in the type of 16q24.3 microdeletion for 12.2%. ConclusionAbnormal manifestations of central nervous system such as language development retardation, learning disabilities, and mental retardation are KBGS-specific phenotypes, which combined with typical craniofacial abnormalities (triangular face, wide eye distance, wide nasal bridge, abnormal philtrum), micrognathia, short and fifth finger bending need to consider ANKRD11 gene mutation. Patients with 16q24.3 microdeletion may be combined with congenital heart disease and ITP.