Case report: Novel deletions in the 6p21.33 involving the CSNK2B gene in patients with Poirier-Bienvenu neurodevelopmental syndrome and literature review

Abstract

Background: Seizures have been identified in most patients with CSNK2B-related Poirer-Bienvenu Neurodevelopment syndrome (POBINDS). Detailed descriptions of seizure phenotypes, various genotypes, and long-term follow-up visits are required for clinicians to provide reasonable clinical management for such patients.

Case summary: We report two new Chinese patients with varying sizes of 6p21.33 deletions encompassing the CSNK2B gene who presented with intellectual disability and seizures. Furthermore, we conducted a literature review of previously reported patients with 6p21.33 deletions or CSNK2B variants. We summarized and analyzed the clinical characteristics of these patients with seizures. The occurrence of a biphasic pattern of epilepsy and pharmacoresistant epilepsy in patients with CSNK2B variants is severely underestimated. One of our patients underwent a long follow-up period and presented with comprehensive disease progression.

Conclusion: Our data suggest that the CSNK2B variant or 6p21.33 deletion should be considered in patients with intellectual disability and epilepsy, especially those characterized by biphasic patterns and digital anomalies.

Keywords: 6p21.33 deletion; CNSK2B; POBINDS; biphasic patterns; digital anomalies; epilepsy.

FIGURE 1

Digital anomalies of patient 1.

FIGURE 2

EEG and Imaging data of patient 1. (A–C) EEG of patient 1 at 20 years old, 23 years old and 24 years old. Background of EEG slows down at 20 years old (A), paroxysmal slow waves lasting for less than 3 s at 23 years old (B), lasting for 20–30 s at 24 years old (C). Progressive slowing of the electroencephalographic (EEG) background is prominent. (D) EEG of patient 1 at 24 years old. The ictal EEG was characterized by right cerebral focus with diffused electrodecremental event, subsequently evolving into bilateral hemispheres. (E) MRI images of patient 1 at 23 years. MRI: revealed abnormal signal in right-sided centrum semiovale.

FIGURE 3

Schematic representation of 6p21.33 deletions in three cases from the UCSC Genome Browser. Gray-shaded area shows the area of 6p21.33 deletion in patient 1. Pink-shaded area shows the area of 6p21.33 deletions in patient 2. Purple-shaded area shows the area of 6p21.33 deletion in patient of Ikuko et al. The black arrow shows CSNK2B gene.