Genetic Epilepsy

Gene: DEPDC5

Green List (high evidence)

PMID: 36067010 - Homozygous missense variants were identified in five families (3x Irish Traveller families with same variant; and 1x Tunisian and 1x Lebanese families with the same variant; ie. 2 different variants only) in 9 children with consistent phenotypic features including extensive bilateral polymicrogyria, congenital macrocephaly, early onset refractory epilepsy and severe developmental delay. Skin biopsy immunohistochemistry suggested hyperactivation of the mTOR pathway. Disease mechanism is LOF as DEPDC5 is a repressor/inhibitor within the mTOR pathway.

PMID: 32848577 - A different homozygous missense variant was identified in a child with focal cortical dysplasia and childhood onset epilepsy.

Created: 6 Oct 2022, 4:09 a.m. | Last Modified: 6 Oct 2022, 4:09 a.m.

Panel Version: 0.1684

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
polymicrogyria; macrocephaly; epilepsy; developmental delay

Publications

• PMID: 36067010
• 32848577

Green List (high evidence)

Familial focal epilepsy with variable foci (FFEVF) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete.

Well established gene-disease association, multiple families.

Created: 6 May 2022, 8:27 a.m. | Last Modified: 6 May 2022, 8:27 a.m.

Panel Version: 0.1592

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy, familial focal, with variable foci 1 MIM#604364

Publications

• 31444548
• 23542697
• 23542701