摘要
目的分析4例PI3K-AKT通路基因变异致巨脑畸形病例临床资料并结合文献复习,为PI3K-AKT通路中基因变异致巨脑畸形疾病的产前诊断提供依据。方法收集云南省第一人民医院收治4例PI3K-AKT通路中基因变异致巨脑畸形的临床资料,检索中国知网、维普、万方及中华医学期刊网及Pubmed等数据库,归纳总结该病的临床表现及特点。结果(1)4例巨脑畸形分别由PI3K-AKT通路中PIK3CA c.1133 G>A、AKT3 c.1393 C>T、PTEN c.254-1 G>T、PIK3CA c.3145 G>A基因变异所致。4例患儿在孕期超声均提示头围明显超孕周生长(>+3SD)伴羊水过多,但仅病例3在产前及时行基因诊断,避免了出生缺陷。(2)通过检索得到32例巨脑畸形病例报道,且PIK3CA基因变异发生率最高,此类疾病多出生后确诊,平均确诊年龄3.5岁。其中出生时巨脑畸形占71.8%,生后肌张力低下、关节松弛(60.0%),皮肤毛细血管畸形改变(53.1%),凉鞋缝脚趾或多指/趾或第二和第三并指/趾(41.9%),后继发头颅MRI Chiari畸形(47.8%),脑室扩张、脑积水(58.0%),智力障碍(35.7%),而在孕期超声头围大报道有25.9%,羊水过多占22.2%。甲状腺功能减退、低血糖等内分泌系统改变可见,发生肿瘤少见。结论PI3K-AKT通路基因变异所致巨脑畸形主要表现为出生后巨脑畸形、肌张力低下、皮肤毛细血管畸形、结缔组织发育异常等,产前诊断率极低。当孕期超声检测提示明显的超孕周并逐渐增大的头围伴羊水过多时,应高度警惕该通路变异所致的巨脑畸形可能。建议在及时完善核型分析、染色体拷贝数变异(copy number variation,CNV)检测时,需进一步行全外显子组测序,提高产前诊断率。
Objective This study aims to provide a basis for prenatal diagnostic of megalencephaly caused by gene variants in the PI3K-AKT pathway by reporting clinical data of 4 cases of this condition and combining liteature review.MethodsThe relevant clinical data of the cases treated in First Peoples Hospital of Yunnan Province was retrieved,the databases of CNKI,VIP,WanFang Database,Chinese Medical Journal Network and Pubmed were summarized,and the clinical manifestations and characteristics of the diseaseweredetermined.Results①4 cases of megalencephaly were attributed to PI3K-AKT pathway gene variants:PIK3CA c.1133 G>A,AKT3 c.1393 C>T,PTEN c.254-1 G>T and PIK3 CA c.3145 G>A.Prenatal ultrasound for all 4 cases indicated significant head circumference enlargement beyond gestational age(>+3SD)accompanied by polyhydramnios.However,only Case 3 underwent timely genetic diagnosis prenatally,preventing birth defects.②A review of 32 reported cases of megalencephaly revealed that PIK3CA gene variants had the highest occurrence rate.Most cases were diagnosed postnatally,with an average age at diagnosis of 3.5 years.Among these,megalencephaly was present at birth in 71.8%of cases,with other features including hypotonia and joint laxity(60.0%),skin capillary malformations(53.1%),sandal gap toes or polydactyly/syndactyly of the second and third toes(41.9%),subsequent Chiari malformations on cranial MRI(47.8%),ventricular enlargement or hydrocephalus(58.0%),and intellectual disabilities(35.7%).Prenatal ultrasound indicated macrocephaly in 25.9%of cases and polyhydramnios in 22.2%.Endocrine abnormalities,such as hypothyroidism and hypoglycemia were observed,while tumor development was rare.Conclusion Megalencephaly caused by gene variants in the PI3K-AKT pathway is primarily characterized by postnatal megalencephaly,hypotonia,skin capillary malformations and connective tissue abnormalities,with a very low prenatal diagnostic rate.When prenatal ultrasound reveals significant and progressively increasing head circumference beyond gestational age along with polyhydramnios,the possibility of megalencephaly caused by PI3K-AKT pathway variants should be highly suspected.It is recommended to complement karyotyping and chromosomal copy number variation(CNV)analysis with whole-exome sequencing to improve the prenatal diagnostic rate.
作者
王娇
章印红
傅友谋
刘小虎
王诗宇
吕涛
买景群
田欢
章锦曼
Wang Jiao;Zhang Yinhong;Fu Youmou;Liu Xiaohu;Wang Shiyu;Lu Tao;Mai Jingqun;Tian Huan;Zhang Jinman(Medical Genetics Department of the First Peoples Hospital of Yunnan Province/Affiliated Hospital of Kunming University of Science and Technology,Key Laboratory Reproductive Health and Birth Defects Prevention and Control in Western China,National Health Commission,Key Laboratory of Birth Defects and Genetic Diseases of Yan Province,Kunming Yunnan 65001l;Department of Obstetrics,Xishui County People's Hospital,Zunyi Guizhou 564600;Department of Medical Genetics,West China Second Hospital of Sichuan University,Chengdu Sichuan 610041,P.R.China)
出处
《中国计划生育和妇产科》
2025年第7期100-105,112,共7页
Chinese Journal of Family Planning & Gynecotokology
基金
2023年云南省“兴滇英才支持计划”(项目编号:XDYC-XLWS-2023-0074)。
