Early onset or syndromic epilepsy

Gene: NEDD4L

Green List (high evidence)

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

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: 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

I don't know

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

Green List (high evidence)

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

• 32117442

Green List (high evidence)

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

• 28515470
• 23934111
• 28212375
• 27694961

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