Early onset or syndromic epilepsy
Gene: NEDD4L
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, noon | Last Modified: 11 Oct 2023, noon
Panel Version: 4.110
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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: Alison Callaway and John Taylor. 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
Some evidence. PMID 27694961 reported 6 unrelated children with delayed psychomotor development apparent since infancy, intellectual disability, and poor or absent speech. Four patients had seizures, including 2 with onset at 4 to 5 months of age.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Periventricular nodular heterotopia 7, 617201
Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least five variants have been reported in cases where seizures are reported (PMIDs:28515470, 27694961, 32117442).Created: 16 Feb 2023, 11:03 a.m. | Last Modified: 16 Feb 2023, 11:03 a.m.
Panel Version: 3.47
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 16 Feb 2023, 10:56 a.m. | Last Modified: 16 Feb 2023, 10:56 a.m.
Panel Version: 3.47
Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 4 variants have been reported in unrelated cases of Periventricular nodular heterotopia 7, 617201 displaying seizures.Created: 3 Sep 2018, 3:58 p.m.
Comment on publications: PMID 23934111 reports one case of 15 year old girl with infantile seizures from 6 months of age, infantile spasms settled by 25 months, with ongoing focal seizures despite multiple trials of treatment (ACTH, VPA, TPM, B6, GBP, ketogenic diet, VGB, LTG, and LEV). PMID 27694961 reports seizures in 3/6 cases with NEDD4L variants.Created: 3 Sep 2018, 3:50 p.m.
Publications
Seizures are a frequently reported feature in this brain development disorder.Created: 24 Jan 2020, 9:51 p.m. | Last Modified: 24 Jan 2020, 9:51 p.m.
Panel Version: 2.0
Seizures are part of the phenotype of this brain development disorder.Created: 17 Aug 2018, 10:50 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Periventricular nodular heterotopia 7, MIM#617201
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q1_23_promote_green was removed from gene: NEDD4L.
Source Expert Review Green was added to NEDD4L. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q1_23_promote_green tag was added to gene: NEDD4L.
Gene: nedd4l has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: NEDD4L were changed from Periventricular nodular heterotopia 7, 617201 to Periventricular nodular heterotopia 7, OMIM:617201; periventricular nodular heterotopia 7, MONDO:0014966
Publications for gene: NEDD4L were set to 28515470; 23934111; 28212375; 27694961
Publications for gene: NEDD4L were set to 27694961; 23934111
Source Wessex and West Midlands GLH was added to NEDD4L.
Source NHS GMS was added to NEDD4L.
Zornitza Stark: Seizures are part of the pheno
Gene: nedd4l has been classified as Amber List (Moderate Evidence).
Publications for gene: NEDD4L were set to 27694961; 23934111
Publications for gene: NEDD4L were set to 27694961; 23934111
Phenotypes for gene: NEDD4L were set to Periventricular nodular heterotopia 7, 617201
Mode of inheritance for gene: NEDD4L was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Expert Review Amber was added to NEDD4L. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to NEDD4L. Panel: Genetic Epilepsy Syndromes
NEDD4L was added to Genetic Epilepsy Syndromes panel. Sources: Radboud University Medical Center, Nijmegen
NEDD4L was created by Sarah Leigh