Beals-Hecht综合征或先天性挛缩蛛网膜畸形(CCA)是一种罕见的,常染色体显性遗传性结缔组织疾病的特征为皱褶的耳朵,arachnodactyly,挛缩,和脊柱侧弯.最近的报道也提到了主动脉根扩张,以前认为可以将这种情况与马凡氏综合征(MFS)区分开来的发现。在许多情况下,这种情况是由纤丝蛋白2基因(FBN2)的突变引起的,迄今为止报道了26个突变,全部位于基因的中间区域(外显子23-34)。我们直接对32位临床诊断为CCA的先证者的整个FBN2基因进行了测序。在14个先证者中,我们发现了13个新的和一个先前描述的FBN2突变,包括外显子17的突变,扩大了CCA中FBN2突变发生的区域。文献综述显示,FBN2阳性患者的表型与所有先前发表的FBN2阳性患者相当。在我们的FBN2阳性患者中,心血管受累包括2例成年患者的二尖瓣脱垂和3例患者的主动脉根部扩大.而扩张在一个先证者中回归,它仍然标记在儿童先证者(z分数:4.09)和他的父亲(z分数:2.94),保证超声心动图随访。我们确认矛盾的髌骨松弛并报告圆锥角膜,肩部肌肉发育不全,肾盂输尿管连接部狭窄为新特征。此外,我们说明了很大的家族内变异性。最后,该队列中的FBN2阴性患者与所有已发表的具有FBN2突变的FBN2阳性患者在临床上没有区别,提示基因座异质性。
Beals-Hecht syndrome or congenital contractural arachnodactyly (CCA) is a rare, autosomal dominant connective tissue disorder characterized by crumpled ears, arachnodactyly, contractures, and scoliosis. Recent reports also mention aortic root dilatation, a finding previously thought to differentiate the condition from Marfan syndrome (MFS). In many cases, the condition is caused by mutations in the fibrillin 2 gene (FBN2) with 26 mutations reported so far, all located in the middle region of the gene (exons 23-34). We directly sequenced the entire FBN2 gene in 32 probands clinically diagnosed with CCA. In 14 probands, we found 13 new and one previously described FBN2 mutation including a mutation in exon 17, expanding the region in which FBN2 mutations occur in CCA.
Review of the literature showed that the phenotype of the FBN2 positive patients was comparable to all previously published FBN2-positive patients. In our FBN2-positive patients, cardiovascular involvement included mitral valve prolapse in two adult patients and aortic root enlargement in three patients. Whereas the dilatation regressed in one proband, it remained marked in a child proband (z-score: 4.09) and his father (z-score: 2.94), warranting echocardiographic follow-up. We confirm paradoxical patellar laxity and report keratoconus, shoulder muscle hypoplasia, and pyeloureteral junction stenosis as new features. In addition, we illustrate large intrafamilial variability. Finally, the FBN2-negative patients in this cohort were clinically indistinguishable from all published FBN2-positive patients harboring a FBN2 mutation, suggesting locus heterogeneity.