Genetic analysis of Poirier Bienvenu neurodevelopmental syndrome associated with CSNK2B variation

Abstract CSNK2B deficiency underlies the pathogenesis of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). In this study, we present four cases of pediatric seizures caused by de novo variants in CSNK2B, with the aim to reinforce the clinical and variant data pertaining to early genetic factors associated with epilepsy. Methods: Trio whole exome sequencing were used to detect variations in the proband and her family members, and bioinformatics annotation was performed for the variation. Sanger sequencing and CSNK2B cDNA sequencing were employed to ascertain the carrier status of additional family members and evaluate the potential impact of variants on splicing. Results: All four children presented with epilepsy as the initial manifestation, accompanied by mild-moderate mental retardation, language and motor developmental delay. Cases 1, 3 and 4 exhibited full-scale tonic-clonic seizures, while case 2 displayed myoclonic and typical absence seizures. Furthermore, case 2 demonstrated delayed growth and development compared to age-matched peers. No abnormality was detected in the head magnetic resonance imaging (MRI). Genetic analysis revealed novel heterozygous variations in the CSNK2B gene in all four children, including c.175 + 1G > A, c.73-2A > G, c.291 + 1G > A and c.481delA. In case 2, reverse transcription analysis of CSNK2B mRNA revealed the retention of the 3' end sequence of Intron 2 and deletion of the 5' end sequence of Exon 3. In treatment, four children received a combination of one to three types of antiepileptic drugs and rehabilitation training individually. Case 1 continued to experience seizures to varying degrees, while cases 2–4 demonstrated effective seizure control. Overall motor and intellectual development improved in all four children, however, there was slow recovery in language function. Conclusion: This study elucidates the molecular etiology of epilepsy in four patients with POBINDS and expands the mutational spectrum of pathogenic variants in the CSNK2B, highlighting their impact on splicing. The highly genetic heterogeneous phenotype of POBINDS relies on the detection of pathogenic variants in CSNK2B. Conventional antiepileptic drugs effectively control seizures, while rehabilitation treatment can significantly improve intelligence and motor function to varying degrees; however, language recovery tends to be relatively slow.