Williams综合征临床诊断和基因缺失的研究

目的 通过临床表现和实验室检查探讨我国主动脉瓣上狭窄（SVAS）患儿中Williams综合征（WS）的诊断标准。方法 对26例因SVAS就诊的患儿，根据Lowery的WS表现型评分表对主要症状进行评分，同时观察患儿一般症状，并采用荧光原位杂交（FISH）技术检测WS相关的弹性蛋白（EIN）基因和LIM激酶1（LIMK1）基因的微缺失。等于4分者3例，小于4分者4例，均未检测到相关基因的缺失。结论 SVAS患儿中，Lowery的WS表现型评分大于4分者可诊断为WS，WS患儿存在EIN基因和LIMK1基因的微缺失。

Clinical features and gene deletions of Williams syndrome

Objective Supravalvular aortic stenosis (SVAS) is a type of leftventricular outflow obstruction. It occurs in three settings: Williams syndrome (WS), autosomal dominant familial cases, and sporadic cases. Most patients with SVAS have WS. WS is a developmental disorder affecting multiple organ systems, involving the vascular, connective tissue, and central nervous systems. This study aimed at discussing the criteria of WS in China by evaluating the clinical features and detecting gene deletions in children clinically diagnosed to have SVAS. Method Twenty-six children (17 males and 9 females) with SVAS who presented to the Xinhua Hospital affiliated to Shanghai Second Medical University and Shanghai Children′s Medical Center between November 1997 and December 1999 were enrolled. These children were followed-up for a median duration of 6.3 (range 1.1 to 19.5) years. Diagnosis of SVAS and non-SVAS congenital heart diseases was based on physical examination, echocardiography, cardiac catheterization and angiography. Mostly the clinical features of WS in these children were assessed according to Lowery′s WS phenotype scoring system, which included typical facial features, mental retardation /developmental delay, SVAS, non-SVAS congenital heart disease, inguinal hernia, and hypercalcemia. All the children also underwent an evaluation of minor medical problems of WS, involving WS personality, weight, head circumference, voice, and ocular, auditory, gastrointestinal, genitourinary, and musculoskeletal organ systems. Fluorescent in situ hybridizations (FISH) were used to detect the microdeletions of elastin (ELN) gene and LIM kinase 1 (LIMK1) gene in all the children. Result Nineteen children, whose WS phenotype scoring was more than 4, showed the gene microdeletions. Children whose scoring was equal to 4 (n=3) or less than 4 (n=4) did not demonstrate deletions. Conclusion These data indicated that WS could be diagnosed in children with SVAS whose Lowery′s scoring was more than 4. Microdeletions of ELN gene and LIMK1 gene were demonstrated in children with WS.