Early onset or syndromic epilepsy

Gene: EIF2B5

I don't know

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

Green List (high evidence)

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. Labuage et al, 2009 - review of 16 patients - 7 had epilepsy (mostly generalised) in 2 affected the provoking factor was named as seizures. 15 patients from 13 unrelated families had mutations in EIF2B5 and one in EIF2B2. 71% had the recurrent R113H variant (9 families hom, 1 family - compound het with a diff missense variant). 3 remaining families all compund het for missense or nonsense variants. Zhang et al, 2015 - 34/36 clinically diagnosed children had a variant identified in the EIF2B genes 12 had EIF2B5 mutations. 16/32 had experienced seizures usually occured 1-2 years after disease onset. Lots of reported variants for this disorder reported and epilepsy seems to arise in ~50% of cases. 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

• 21484434

Green List (high evidence)

Seizures are a feature of this leukodystrophy.

Created: 13 Aug 2018, 11:37 a.m.

Phenotypes
Leukoencephalopathy with vanishing white matter, MIM#603896

Variants in this GENE are reported as part of current diagnostic practice