Genetic Epilepsy

Gene: CSNK2B

Green List (high evidence)

3 probands (2 confirmed de novo) with missense variants affecting Asp32 (p.Asp32His, p.Asp32Asn), which have an intellectual disability-craniodigital syndrome (IDCS) distinct from Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). Functional assays demonstrated the variants upregulated protein expression and lead to WNT signalling dysregulation. The mechanism of disease appears to be dominant-negative for IDCS, whereas the mechanism for POBINDS is loss-of-function.

Created: 7 Jun 2022, 10:50 p.m. | Last Modified: 7 Jun 2022, 10:50 p.m.

Panel Version: 1.63

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Craniodigital syndrome-intellectual disability syndrome MONDO:0015463

Publications

• 35571680

Mode of pathogenicity
Other

Green List (high evidence)

At least 3 unrelated families reported.

Created: 24 Jan 2022, 9:25 a.m. | Last Modified: 24 Jan 2022, 9:25 a.m.

Panel Version: 0.1427

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732

Publications

• 28585349
• 28762608

Green List (high evidence)

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.

Created: 21 Dec 2021, 5:50 a.m. | Last Modified: 21 Dec 2021, 5:50 a.m.

Panel Version: 0.1413

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
genetic epilepsy; developmental delay; intellectual disability

Publications

• PMID: 34041744 DOI: 10.1111/epi.16931