Abstract
Introduction: The Lysine Demethylase 5C gene (KDM5C), located at 11p22, is a crucial gene implicated in X-linked intellectual disability (ID), also known as Claes Jensen syndrome. Mutations in the KDM5C gene can negatively impact H3K4me2/3 modifications, leading to a significant reduction in brain-derived neurotrophic factor (BDNF) and sodium voltage-gated channel alpha subunit 2 (SCN2A), which are associated with both autistic spectrum disorder (ASD) and cognitive impairment. Case Presentation: This study presents a novel KDM5C mutation [rs1569278313, Xp.11.22 (GRCh37); c.807delC exon7/25; Pro269fs], a frameshift deletion at the N terminus in exon 7, in a 7-year-old boy with a history of hypothyroidism and left-hand polydactyly. The primary complaints included seizures, short stature, speech difficulties, restlessness, gait problems, and ID. A brain computerized tomography (CT) scan was normal, while magnetic resonance imaging (MRI) revealed bilateral cerebellar hemisphere atrophy. Multifocal epileptic discharges were observed in the electroencephalogram (EEG), and the auditory brainstem response (ABR) was unremarkable. whole exome sequencing (WES) identified a pathogenic frameshift deletion in the KDM5C gene. Conclusions: This case features a frameshift deletion in exon 7 of the KDM5C gene, manifesting as a syndromic face, short stature, and global developmental delay. Additionally, we discuss the rare KDM5C syndromic features in this patient, providing valuable insight into the pathogenicity and clinical implications of this mutation.