Medical Genetics Unit, IRCCS Bambino Gesù Children Hospital, Rome, Italy.
Clinical and Experimental Neurology, IRCCS Bambino Gesù Children Hospital, Rome, Italy.
Clin Genet. 2023 Nov;104(5):528-541. doi: 10.1111/cge.14404. Epub 2023 Jul 17.
CTNNB1 [OMIM *116806] encodes β-catenin, an integral part of the cadherin/catenin complex, which functions as effector of Wnt signaling. CTNNB1 is highly expressed in brain as well as in other tissues, including heart. Heterozygous CTNNB1 pathogenic variations are associated with a neurodevelopmental disorder characterized by spastic diplegia and visual defects (NEDSDV) [OMIM #615075], featuring psychomotor delay, intellectual disability, behavioral disturbances, movement disorders, visual defects and subtle facial and somatic features. We report on a new series of 19 NEDSDV patients (mean age 10.3 years), nine of whom bearing novel CTNNB1 variants. Notably, five patients showed congenital heart anomalies including absent pulmonary valve with intact ventricular septum, atrioventricular canal with hypoplastic aortic arch, tetralogy of Fallot, and mitral valve prolapse. We focused on the cardiac phenotype characterizing such cases and reviewed the congenital heart defects in previously reported NEDSDV patients. While congenital heart defects had occasionally been reported so far, the present findings configure a higher rate of cardiac anomalies, suggesting dedicated heart examination to NEDSDV clinical management.
CTNNB1 [OMIM *116806] 编码 β-连环蛋白，它是钙粘蛋白/连环蛋白复合物的一个组成部分，作为 Wnt 信号的效应物发挥作用。CTNNB1 在大脑以及其他组织中高度表达，包括心脏。杂合性 CTNNB1 致病性变异与以痉挛性双瘫和视觉缺陷为特征的神经发育障碍（NEDSDV）[OMIM #615075]相关，其特征为精神运动发育迟缓、智力残疾、行为障碍、运动障碍、视觉缺陷和细微的面部和躯体特征。我们报告了一系列 19 例新的 NEDSDV 患者（平均年龄 10.3 岁），其中 9 例携带新的 CTNNB1 变体。值得注意的是，有 5 例患者出现先天性心脏异常，包括肺动脉瓣缺如伴完整室间隔、房室管伴主动脉弓发育不全、法洛四联症和二尖瓣脱垂。我们关注这些病例的心脏表型，并回顾了以前报道的 NEDSDV 患者的先天性心脏病缺陷。虽然目前已经有关于先天性心脏病缺陷的报道，但目前的发现显示出更高的心脏异常发生率，这提示在 NEDSDV 临床管理中应进行专门的心脏检查。
