Early onset or syndromic epilepsy

Gene: IFIH1

Green List (high evidence)

Aicardi-Goutieres syndrome is associated with seizures. AD Aicardi Goutieres Syndrome 7 (AGS7) and AD Singleton-Merton syndrome 1 (SGMRT1). AGS7 - Oda et al, 2014 2/3 unrelated Japanese boys also presented with seizures - all had de novo het missense variants and some functional work done into all 3 variants. Rice et al, 2004 - 8 children with a neurodevelopmental disorder - 8 diff missense varints identified, 6 de novo, 1 not known and 1 inherited from clinically unaff father and grandmother. 1/8 reported to have seizures. Crow et al, 2014 - An individual with HSP who had a de novo missense variant in this gene. SGMRT1 - characterised by abnormalities of blood vessels, teeth and bone - Seizures/epilepsy are not a feature. Seizures seen in 3/12 patients.

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
Aicardi-Goutieres syndrome, 615846; Singleton-Merten syndrome, 182250

Publications

• 24686847
• 24995871

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

Comment on list classification: Updated rating from Amber to Green. Green review and confirmed DD-G2P gene for Aicardi-Goutieres syndrome 7, which can present with seizures. Seizures reported in PMID:24995871, PMID:24686847 and 29270977 (note some cases are febrile seizures). Since seizures are a recognised phenotype for Aicardi-Goutieres syndrome (reported by e.g. PMID:25604658), and other AGS-associated genes are on the panel, it is reasonable to include IFIH1 on this panel.

Created: 8 Nov 2018, 9:21 a.m.

PMID:24686847 (Rice et al. 2014) observed six rare IFIH1 variants in eight probands with AGS. 2 of the patients presented with seizures (see Supplementary material): F102 (European Italian male with R720Q variant) and F626 (European Italian male with D393V variant).

Created: 8 Nov 2018, 9:16 a.m.

PMID:29270977 report a 7 year old Japanese girl with febrile seizures amongst her phenotypes and a novel IFIH1 variant.

Created: 8 Nov 2018, 9:08 a.m.

PMID:25604658 (Crow et al. 2015) reported on 374 patients from 299 families with symptoms including seizures in 140 patients. Monoallelic variants of IFIH1 were found in 9 families.

Created: 8 Nov 2018, 9:08 a.m.

PMID:29239743 (Mutairi et al., 2018) reviewed the records of 24 unrelated patients with Aicardi-Goutières syndrome from 6 tertiary hospitals in different Arab countries. The most common presenting signs were developmental delay and seizures. A Heterozygous c.961G>T variant in IFIH1 was found in 1 patient who didn't have seizures as part of her phenotype.

Created: 8 Nov 2018, 9:08 a.m.

Oda et al 2014 (PMID:24995871) report IFIH1 variants in 3 unrelated Japanese patients with AGS7. 2 individuals had complex febrile seizures.

Created: 8 Nov 2018, 9:08 a.m.

Green List (high evidence)

Seizures are a feature of this multi-system disorder.

Created: 16 Aug 2018, 12:45 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Aicardi-Goutieres syndrome 7, MIM#615846

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