Early onset or syndromic epilepsy
Gene: WDR45B
At least three unrelated families reported (five in total), majority of individuals have had seizures, this gene fulfils criteria for Green rating.Created: 26 Jan 2020, 6:53 a.m. | Last Modified: 26 Jan 2020, 6:53 a.m.
Panel Version: 2.0
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, MIM# 617977
Publications
Variants in this GENE are reported as part of current diagnostic practice
AR Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures (are in most patients). 1 missense and 2 nonsense reported on HGMD - 1 of these (nonsense) mentions epilepsy very small numbers. Suleiman et al, 2018.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
Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977
Publications
Added 'for-review' tag based on Zornitza's Green review on a gene where an Amber rating was decided at the last GLH review. Of the publications listed, PMID:28503735 (Suleiman et al) report 3 families (2 with seizures). PMID:21937992. Najmabadi et al 2011 identify WDR45B (WDR45L) as a candidate gene for ID. PMID:27431290 (Anazi et al., 2017) identified likely pathogenic alleles in WDR45B in ID individuals. Little information provided about WDR45B phenotype.Created: 26 May 2020, 2:46 p.m. | Last Modified: 26 May 2020, 2:46 p.m.
Panel Version: 2.60
As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.Created: 15 Aug 2019, 9:39 a.m. | Last Modified: 15 Aug 2019, 9:39 a.m.
Panel Version: 1.227
Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary, the evidence is borderline: PMID:28503735 (Suleiman et al) report 6 individuals from 3 families with homozygous pathogenic variants in WDR45B, and 2 of the families (5 indivs) had seizures- seizures were not reported in the sole individual from family 3.Created: 15 Aug 2019, 9:39 a.m. | Last Modified: 15 Aug 2019, 9:39 a.m.
Panel Version: 1.227
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: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on phenotypes: Now (July 9th 2019) associated with a disorder in OMIM (617977).Created: 9 Jul 2019, 3:52 p.m. | Last Modified: 9 Jul 2019, 3:52 p.m.
Panel Version: 1.145
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.
Panel Version: 2.491
Not associated with phenotype in OMIM, but as a possible G2P. At least three variants have now been reported as homozygotes in at least three families, in individuals with profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations.Created: 12 Jun 2017, 12:58 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
individuals with profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations
Publications
Tag for-review was removed from gene: WDR45B.
Source Expert Review Green was added to WDR45B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: WDR45B were changed from Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977; profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations to Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, OMIM:617977
Tag for-review tag was added to gene: WDR45B.
Publications for gene: WDR45B were set to 21937992; 28503735
Gene: wdr45b has been classified as Amber List (Moderate Evidence).
Gene: wdr45b has been classified as Amber List (Moderate Evidence).
Source Wessex and West Midlands GLH was added to WDR45B.
Source NHS GMS was added to WDR45B.
Phenotypes for gene: WDR45B were changed from profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations to Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977; profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations
Sarah Leigh: Not associated with phenotype
Victorian Clinical Genetics Services was added to WDR45B. Panel: Genetic Epilepsy Syndromes
WDR45B was added to Genetic Epilepsy Syndromes panel. Sources: Literature,Expert Review Green
WDR45B was created by Sarah Leigh