Shaheen Manal M, Mujahed Ramzi H, Abusabha Saja E, Alwahsh Iman M, Abufara Areen A, Junaidi Leen J, Alkablan Haya A
Faculty of Medicine, Polytechnic University, Hebron, 00970, Palestine.
Department of Pediatrics, Hebron Governmental Hospital, Hebron, Palestine.
BMC Pediatr. 2025 May 9;25(1):368. doi: 10.1186/s12887-025-05709-2.
Claes-Jensen syndrome (CJS) is a rare X-linked intellectual disability caused by mutations in the KDM5C gene, encoding a histone demethylase involved in chromatin remodeling and neurodevelopment. Males with hemizygous mutations in KDM5C present with intellectual disability, dysmorphism, and neurodevelopmental delays. Mutations, either maternally transmitted or de novo, account for 0.7-2.8% of X-linked intellectual impairments. This case reports a rare de novo variant in the KDM5C gene in a Palestinian male patient, contributing to the limited literature on this condition.
We present a 2-year and 10-month-old Palestinian male with developmental regression following an acute viral illness at 22 months. This included the loss of the ability to walk, developmental delays, and persistently elevated lactic acid. Genetic testing, including trio-based whole-exome sequencing, identified a de novo KDM5C mutation (c.2827 C > T p.Arg943), confirming the diagnosis of Claes-Jensen syndrome. Neuroimaging showed faint hyperintensities in the posterior periventricular white matter, suggestive of dysmyelination.
This case highlights the diagnostic challenges of CJS and the importance of genetic testing in neurodevelopmental disorders. Early recognition aids in symptomatic management and improves clinical understanding of this rare condition. Our report adds new insight into the clinical spectrum of CJS and emphasizes the need for heightened awareness among clinicians.
克莱斯 - 延森综合征（CJS）是一种罕见的X连锁智力障碍，由KDM5C基因突变引起，该基因编码一种参与染色质重塑和神经发育的组蛋白去甲基化酶。KDM5C基因半合子突变的男性表现为智力障碍、畸形和神经发育迟缓。无论是母系遗传还是新发突变，都占X连锁智力障碍的0.7 - 2.8%。本病例报告了一名巴勒斯坦男性患者KDM5C基因中一种罕见的新发变异，为关于这种疾病的有限文献增添了内容。
我们报告一名2岁10个月大的巴勒斯坦男性，在22个月时患急性病毒感染疾病后出现发育倒退。这包括失去行走能力、发育迟缓以及乳酸持续升高。基因检测，包括基于三联体的全外显子组测序，发现了一个新发的KDM5C突变（c.2827 C>T p.Arg943），确诊为克莱斯 - 延森综合征。神经影像学显示脑室周围后白质有轻微高信号，提示髓鞘形成异常。
本病例突出了克莱斯 - 延森综合征的诊断挑战以及基因检测在神经发育障碍中的重要性。早期识别有助于进行症状管理并增进对这种罕见疾病的临床理解。我们的报告为克莱斯 - 延森综合征的临床谱提供了新的见解，并强调临床医生需要提高认识。
