韦弗综合征,1974年首次描述,其特点是身材高大,典型的面部外观,和可变的智力残疾。2011年,组蛋白甲基转移酶发生突变,EZH2被证明会导致韦弗综合征。迄今为止,我们已经确定了48例EZH2突变的个体。突变主要是整个基因发生的错义突变,在SET域中进行一些聚类(12/48)。截短突变并不常见(4/48),仅在最后一个外显子中发现,在SET域之后。通过对EZH2突变阳性个体的临床数据和面部照片的分析,我们已经表明,面部特征可以是微妙的,韦弗综合征的临床诊断因此是具有挑战性的,尤其是老年人。然而,身材高大是很常见的,在>90%的受影响个体中报告。智力残疾也很常见,目前在~80%,但变化很大,通常很温和。其他临床特征可能有助于将个体分层以进行EZH2突变测试,包括camptodactyly,软,生面团的皮肤,脐疝,和一个低,嘶哑的哭声.Sotos和Weaver综合征之间的表型重叠也很明显。因此,EZH2突变的鉴定可以提供确认Weaver综合征的微妙表现和/或区分Weaver和Sotos综合征的客观手段。随着突变检测变得越来越容易,并且识别出更多的EZH2突变阳性个体,应提高对EZH2突变的临床谱和预后影响的认识.
Weaver syndrome, first described in 1974, is characterized by tall stature, a typical facial appearance, and variable intellectual disability. In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome. To date, we have identified 48 individuals with EZH2 mutations. The mutations were primarily missense mutations occurring throughout the gene, with some clustering in the SET domain (12/48). Truncating mutations were uncommon (4/48) and only identified in the final exon, after the SET domain. Through analyses of clinical data and facial photographs of EZH2 mutation-positive individuals, we have shown that the facial features can be subtle and the clinical diagnosis of Weaver syndrome is thus challenging, especially in older individuals. However, tall stature is very common, reported in >90% of affected individuals. Intellectual disability is also common, present in ~80%, but is highly variable and frequently mild. Additional clinical features which may help in stratifying individuals to EZH2 mutation testing include camptodactyly, soft, doughy skin, umbilical hernia, and a low, hoarse cry. Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. As mutation testing becomes increasingly accessible and larger numbers of EZH2 mutation-positive individuals are identified, knowledge of the clinical spectrum and prognostic implications of EZH2 mutations should improve.