Early onset or syndromic epilepsy
Gene: EIF2B2
AR ovarioleukodystrophy and Leukoencephalopathy with vanishing white matter (VWM). Can also be caused by mutations in any of the 5 genes encoding subunits of the translation initiation factor EIF2B (EIF2B1,2,3,4 or 5). It is a neurologic disorder characterised by variable neurological features including progressive cerebellar ataxia, spasticity and cognitive impairement assoc with white matter lesions on brain imaging. Onset from early infancy to adulthood. Episodes of deterioration followed infections and minor head traumas. Shimada et al 2012 - 11 month old also had intractable epilepsy triggered by infections - submicroscopic del of 14q24.3 - 25 genes in this region including EIF2B2 including a missense change in this gene. Shimada et al, 2015 - variants in 6 patients (4 unrelated individ and 2 siblings) in EIF2B genes: 5/6 had seizures - 4 families of these 2 unrelated individuals one hom and one compound het for EIF2B2 missense variants. 1 aff was hom for an EIF2B1 variant. 1 aff was compound het for an EIF2B5 mutation and the two sibs were compound het for EIF2B4 mutations - 1 had epilepsy, 1 didn't.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leukoencephalopathy with vanishing white matter, 603896; Ovarioleukodystrophy, 603896
Publications
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Updated rating from Amber to Green: Green review from Zornitza. Seizures are seen in some patients with Vanishing White Matter Disease (VWM). Sufficient cases of seizures in patients from the literature (2 in PMID:25843247 and 1 in PMID:22678813) for inclusion on the panel.Created: 27 Nov 2018, 8:34 p.m.
Shimada et al, 2012 (PMID:22678813) report an 11-month-old patient with intractable epilepsy amongst her symptoms. A Submicroscopic deletion at 14q24.3 that included EIF2B2 was found in compound heterozygous state for a missense variant in EIF2B2 (V85W). The p.V85E variant may be common in individuals of E. Asian origin (Chinese and Japanese).Created: 27 Nov 2018, 8:32 p.m.
Shimada et al. (2015, PMID:25843247) analysed genes encoding all five subunits of EIF2B in 22 patients tentatively diagnosed with Vanishing White Matter Disease (VWM). Unrelated patients 2 and 3 had variants in EIF2B2; homozygous c.254T>A (p.V85E) in patient 2, and c.254T>A (p.V85E) and c.682A>G (p.R228G) in compound heterozygosity in patient 3. Both patients had seizures amongst their phenotypes.Created: 27 Nov 2018, 8:31 p.m.
Seizures are a feature of this leukodystrophy.Created: 13 Aug 2018, 11:33 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leukoencephalopathy with vanishing white matter, MIM#603896
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to EIF2B2.
Source NHS GMS was added to EIF2B2.
Zornitza Stark: Seizures are a feature of this
Publications for gene: EIF2B2 were set to
Gene: eif2b2 has been classified as Green List (High Evidence).
Gene: eif2b2 has been classified as Green List (High Evidence).
Mode of inheritance for gene: EIF2B2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B2 were changed from to Leukoencephalopathy with vanishing white matter, 603896
Expert Review Amber was added to EIF2B2. Panel: Genetic Epilepsy Syndromes
EIF2B2 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
EIF2B2 was created by Sarah Leigh