Two Siblings With Al Kaissi Syndrome: Clinical, Radiological, and Molecular Characterization of Compound Heterozygous CDK10 Variants.

Abstract

Al Kaissi syndrome is a rare autosomal recessive neurodevelopmental disorder resulting from biallelic loss-of-function variants in the CDK10 gene. Cyclin-dependent kinase 10 (CDK10) encoded protein plays essential roles in cell cycle regulation, transcriptional control, and ciliogenesis. We report two male siblings presenting with developmental delay, dysmorphic facial features, and skeletal anomalies. Comprehensive clinical, radiological, and molecular genetic evaluations were performed on the affected individuals and their parents, including exome sequencing. Both siblings were found to carry compound heterozygous pathogenic variants in CDK10: a previously reported splice-site variant (c.609-1G > A) and a frameshift variant (c.520_521del), previously unreported in clinical cases. The clinical phenotype in both cases was consistent with Al Kaissi syndrome, including intellectual disability, facial dysmorphisms, spinal malformations, and delayed developmental milestones. This report presents the first Turkish cases of Al Kaissi syndrome with compound heterozygous CDK10 variants and thoroughly reviews previously reported cases. This expands the known phenotypic and genotypic spectrum of the disorder.