Early onset or syndromic epilepsy

Gene: PI4K2A

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:59 p.m. | Last Modified: 24 Feb 2025, 5:59 p.m.

Panel Version: 7.39

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: As reviewed by Tracy Lester, there are four unrelated cases reported with a neurodevelopmental disorder. Of these, epilepsy was present in three unrelated cases. Hence, this gene should be promoted to green rating in the next GMS update.

Created: 5 Nov 2024, 12:36 p.m. | Last Modified: 5 Nov 2024, 12:36 p.m.

Panel Version: 7.3

Comment on phenotypes: This gene has been associated with relevant phenotype in OMIM (MIM #620732), but not yet in Gene2Phenotype.

Created: 5 Nov 2024, 12:11 p.m. | Last Modified: 5 Nov 2024, 12:11 p.m.

Panel Version: 8.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732

Green List (high evidence)

At least three cases have been reported with biallelic variants in this gene and a neurodevelopmental disorder
35880319 - Two patients with PI4K2A deficiency (homozygous variants) were identified by exome sequencing, presenting with developmental and epileptic-dyskinetic encephalopathy. Neuroimaging showed corpus callosum dysgenesis, diffuse white matter volume loss, and hypoplastic vermis. In addition to NDD, we observed recurrent infections and death at toddler age.
30564627 - We report a family of Saudi Arabian ancestry with two children presenting with global developmental delay, dystonia, disturbed sleep, and heat intolerance. By genome sequencing, we identified a nonsense variant in the first exon of PI4K2A that was homozygous in both affected individuals and was absent from, or heterozygous in, seven unaffected siblings.
32418222 - a homozygous missense variant of uncertain significance was suggested to be responsible for some features in a case with NDD and metabolic cutis laxa.
Sources: NHS GMS

Created: 4 Nov 2024, 4:06 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; developmental delay; seizures

Publications

• 30564627
• 35880319
• 32418222