携带 CSNK2A1 基因杂合致病性变异的患者:更新 Okur-Chung 神经发育综合征的新病例。

Patient with a heterozygous pathogenic variant in CSNK2A1 gene: A new case to update the Okur-Chung neurodevelopmental syndrome.

机构信息

Service de génétique clinique, CHRU de Nancy, Nancy, France.

Laboratoire de génétique médicale, CHRU Nancy, Nancy, France.

出版信息

Am J Med Genet A. 2024 Sep;194(9):e63642. doi: 10.1002/ajmg.a.63642. Epub 2024 May 6.

Abstract

The autosomal dominant Okur-Chung neurodevelopmental syndrome (OCNDS: OMIM #617062) is a rare neurodevelopmental disorder first described in 2016. Features include developmental delay (DD), intellectual disability (ID), behavioral problems, hypotonia, language deficits, congenital heart abnormalities, and non-specific dysmorphic facial features. OCNDS is caused by heterozygous pathogenic variants in CSNK2A1 (OMIM *115440; NM_177559.3). To date, 160 patients have been diagnosed worldwide. The number will likely increase due to the growing use of exome sequencing (ES) and genome sequencing (GS). Here, we describe a novel OCNDS patient carrying a CSNK2A1 variant (NM_177559.3:c.140G>A; NP_808227.1:p.Arg47Gln). Phenotypically, he presented with DD, ID, generalized hypotonia, speech delay, short stature, microcephaly, and dysmorphic features such as low-set ears, hypertelorism, thin upper lip, and a round face. The patient showed several signs not yet described that may extend the phenotypic spectrum of OCNDS. These include prenatal bilateral clubfeet, exotropia, and peg lateral incisors. However, unlike the majority of descriptions, he did not present sleep disturbance, seizures or gait difficulties. A literature review shows phenotypic heterogeneity for OCNDS, whether these patients have the same variant or not. This case report is an opportunity to refine the phenotype of this syndrome and raise the question of the genotype-phenotype correlation.

摘要

常染色体显性遗传的 Okur-Chung 神经发育综合征(OCNDS:OMIM #617062)是一种罕见的神经发育障碍,于 2016 年首次描述。其特征包括发育迟缓(DD)、智力障碍(ID)、行为问题、低张力、语言缺陷、先天性心脏异常和非特异性的发育不良面部特征。OCNDS 是由 CSNK2A1 中的杂合致病性变异引起的(OMIM *115440;NM_177559.3)。迄今为止,全世界已诊断出 160 名患者。由于外显子组测序(ES)和基因组测序(GS)的使用越来越多,这个数字可能会增加。在这里,我们描述了一名患有 CSNK2A1 变异的新型 OCNDS 患者(NM_177559.3:c.140G>A;NP_808227.1:p.Arg47Gln)。表型上,他表现为 DD、ID、全身低张力、言语延迟、身材矮小、小头畸形和发育不良特征,如低位耳、远视、薄上唇和圆脸。该患者表现出一些尚未描述的体征,可能会扩展 OCNDS 的表型谱。这些包括产前双侧马蹄内翻足、外斜视和钉状侧切牙。然而,与大多数描述不同的是,他没有出现睡眠障碍、癫痫发作或步态困难。文献综述显示,OCNDS 的表型存在异质性,无论这些患者是否具有相同的变异。本病例报告为完善该综合征的表型提供了机会,并提出了基因型-表型相关性的问题。

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