Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Department of Pediatric Neurology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Eur J Paediatr Neurol. 2022 Nov;41:91-98. doi: 10.1016/j.ejpn.2022.11.003. Epub 2022 Nov 12.
Vici syndrome (OMIM 242840) is a very rare autosomal recessive multisystem disorder first described in 1988. In 2013, bi-allelic loss-of-function mutations in EPG5 were reported to cause Vici syndrome. Five principal diagnostic features of Vici syndrome have been proposed: agenesis of the corpus callosum, cataracts, cardiomyopathy, hypopigmentation, and combined immunodeficiency. We identified 15 patients carrying a homozygous founder missense variant in EPG5 who all exhibit a less severe clinical phenotype than classic Vici syndrome. All 15 show typical brain abnormalities on MRI. The homozygous founder variant in EPG5 they carry results in a shorter in-frame transcript and truncated, but likely still residual, EPG5 protein. We speculate that the residual EPG5 protein explains their attenuated phenotype, which is consistent with two previous observations that low expression of EPG5 can lead to an attenuated Vici syndrome phenotype. We propose renaming this condition EPG5-related neurodevelopmental disorder to emphasize the clinical variability of patients with bi-allelic mutations in EPG5.
Vici 综合征（OMIM 242840）是一种非常罕见的常染色体隐性多系统疾病，于 1988 年首次描述。2013 年，报道了 EPG5 的双等位基因功能丧失突变可导致 Vici 综合征。提出了 Vici 综合征的五个主要诊断特征：胼胝体发育不全、白内障、心肌病、色素减退和联合免疫缺陷。我们鉴定了 15 名携带 EPG5 纯合起始错义变异的患者，他们均表现出比经典 Vici 综合征更轻的临床表型。所有 15 名患者的 MRI 均显示出典型的脑异常。他们携带的 EPG5 纯合起始错义变异导致较短的框内转录本和截断的，但可能仍然残留的 EPG5 蛋白。我们推测残留的 EPG5 蛋白解释了他们的减轻表型，这与之前的两项观察结果一致，即 EPG5 的低表达可导致 Vici 综合征表型减轻。我们建议将这种情况重新命名为 EPG5 相关神经发育障碍，以强调 EPG5 双等位基因突变患者的临床变异性。
