Early onset or syndromic epilepsy

Gene: FBXO28

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 9:39 a.m. | Last Modified: 1 Feb 2023, 9:39 a.m.

Panel Version: 3.29

Green List (high evidence)

Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least six variants have been reported in at least six cases. In one of these cases the variant was inherited from the unanaffected mother, who was mosaic (PMID: 33280099), otherwise the variants were de novo heterozygotes (PMIDs: 30160831; 33280099).

Created: 25 Aug 2022, 4:34 p.m. | Last Modified: 25 Aug 2022, 4:34 p.m.

Panel Version: 2.579

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 25 Aug 2022, 4:26 p.m. | Last Modified: 25 Aug 2022, 4:26 p.m.

Panel Version: 2.579

Green List (high evidence)

Nine new individuals with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and all 10 known cases reviewed to delineate the phenotypic spectrum. All had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features.
Sources: Literature

Created: 9 Dec 2020, 8:33 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental and epileptic encephalopathy

Publications

• 33280099