Pathogenic KMT2E variants underly Oapos;Donnell-Luria-Rodan syndrome, a recently described neurodevelopmental disorder characterized by global developmental delay, variable degrees of intellectual disability, and subtle facial dysmorphism. Less common findings include autism, seizures, gastrointestinal (GI) problems, and abnormal head circumference. Occurrence of mostly truncating variants as well as the similar phenotype observed in individuals with deletions spanning KMT2E suggest haploinsufficiency of this gene as a common mechanism for the disorder, while a gain-of-function or dominant-negative effect cannot be ruled out for some missense variants. Deletions reported in the literature encompass several additional known or presumed haploinsufficient genes, thus leading to more complex phenotypes. Here, we describe a male with antenatal onset hydronephrosis, hypotonia, global developmental delay, prominent GI symptoms as well as facial dysmorphism. Chromosomal microarray revealed a 239-kb de novo microdeletion spanning KMT2E and LHFPL3. Clinical presentation of our proband, harboring one of the smallest deletions of the region confirms the core features of this disorder, suggests GI symptoms as a prominent finding in affected individuals while expanding the phenotypic spectrum to abnormalities of the urinary tract.
Mol Syndromol

中文翻译：

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发育迟缓儿童中跨越 KMT2E 的 239-kb 微缺失：表型的进一步描述

致病性KMT2E变异是 Oapos;Donnell-Luria-Rodan 综合征的基础，这是一种最近描述的神经发育障碍，其特征是整体发育迟缓、不同程度的智力障碍和轻微的面部畸形。不太常见的症状包括自闭症、癫痫、胃肠道 (GI) 问题和头围异常。大多数截短变异的出现以及在KMT2E缺失个体中观察到的相似表型表明该基因的单倍体不足是该疾病的常见机制，同时不能排除某些错义的功能获得或显性失活效应变种。文献中报道的缺失包括几个额外的已知或推测的单倍体不足基因，从而导致更复杂的表型。在这里，我们描述了一名患有产前肾积水、肌张力低下、整体发育迟缓、明显胃肠道症状以及面部畸形的男性。染色体微阵列显示跨越KMT2E和LHFPL3的 239 kb 从头微缺失。我们的先证者的临床表现，具有该区域最小的缺失之一，证实了这种疾病的核心特征，表明胃肠道症状是受影响个体的一个突出发现，同时将表型谱扩展到泌尿道异常。
摩尔综合症