Early onset or syndromic epilepsy

Gene: NCDN

I don't know

Comment on list classification: Rating Amber with monoallelic MOI, awaiting further cases with seizures (2/3 de novo cases with epilepsy - PMID: 33711248). Currently 'Red' evidence level for biallelic form.

Created: 30 Apr 2021, 10:55 a.m. | Last Modified: 30 Apr 2021, 10:55 a.m.

Panel Version: 2.333

Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline if this gene is upgraded to Green on this panel in the future.

Created: 30 Apr 2021, 10:52 a.m. | Last Modified: 30 Apr 2021, 10:56 a.m.

Panel Version: 2.333

NCDN is not yet associated with any phenotype in OMIM (last edited on 08/08/2012) but in Gene2Phenotype monoallelic disease has a 'probable' confidence rating while biallelic variants have a 'possible' disease confidence rating.

- PMID: 33711248 (2021) - Six affected individuals (3 sibs with homozygous missense, and 3 unrelated patients with different de novo missense variants) with variable degrees of DD, ID, and seizures. All 3 sibs had generalised seizures (fever induced in 2), while 2/3 individuals with heterozygous variants developed epileptic spasms presenting several times per day prior to treatment. Supportive functional data included.
Sources: Literature

Created: 30 Apr 2021, 10:51 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Intellectual disability; epilepsy

Publications

• 33711248