Early onset or syndromic epilepsy

Gene: SETD5

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).

Created: 20 Oct 2020, 2:09 p.m. | Last Modified: 20 Oct 2020, 2:09 p.m.

Panel Version: 2.184

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

Comment on list classification: Review article PMID 29484850 reports seizures in 10/42 (23.8%) cases of autism spectrum disorders carrying heterozygous SETD5 variants.

Created: 1 Jun 2020, 5:25 p.m. | Last Modified: 1 Jun 2020, 5:25 p.m.

Panel Version: 2.84

Green List (high evidence)

PMID: 29484850: Review of all literature reporting SETD5 (table 1). Out of 42 patients described in these papers, 71.4% have motor impairment/delay, 69.0% speech impairment/delay, 23.8% eplilepsy/seizures, 38% congenital heart defects, 95.2% facial dysmorphism, 21.4% hand stereotypies/ritualised behaviour, 19% impaired vision, 42.8% muscle hypotonia and 28.6% polydactyly.

Considering nearly a quarter of all reported individuals with this neurodevelopmental syndrome have epilepsy/seizures, we have rated this gene Green on our epilepsy panel.

Created: 25 Jan 2020, 4:19 a.m. | Last Modified: 25 Jan 2020, 4:19 a.m.

Panel Version: 2.0

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability, autosomal dominant 23 (MIM # 615761)

Publications

• 29484850

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

I don't know

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, 9:38 a.m. | Last Modified: 15 Aug 2019, 9:38 a.m.

Panel Version: 1.226

Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: although four reviewers agreed it should be on EE panel, there is limited evidence of a seizure phenotype. PMID:26482601: (Kobayashi et al., 2016) examined 11 patients with early-onset epileptic encephalopathy, and SETD5 variants were amongst the findings. Therefore consider demoting SETD5.

Created: 15 Aug 2019, 9:37 a.m. | Last Modified: 15 Aug 2019, 10:29 a.m.

Panel Version: 1.236

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

I don't know

AD mental retardation - no mention of seizures as a clinical feature on OMIM. Panel app - have as a green gene seems to be due to it being in an EIEE panel?? On HGMD pro one mention of a mutation assoc with dev delay, seizures, delayed speech and dysmorphic features - Halvardson et al 2016 - opened paper and the SETD5 variant was in a patient with AD MR. Don't add to panel.

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
Mental retardation, 615761

Publications

• 25138099
• 24680889

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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

Comment when marking as ready: Confirmed DD gene and all 4 reviewers agree this should be green. Mode of inheritance and loss-of-function mechanism confirmed.

Created: 21 Jan 2016, 12:59 p.m.

Comment on phenotypes: Source: OMIM

Created: 21 Jan 2016, 12:57 p.m.

Comment on mode of inheritance: Confirmed and not on imprinted gene list.

Created: 21 Jan 2016, 12:57 p.m.