Early onset or syndromic epilepsy

Gene: FGF12

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

Green List (high evidence)

AD EIEE47 - onset of intractable seizures in the first few days or weeks of life. Siekierska et al, 2016 - 2 sibs with EIEE deaths at 7 and 3.5 years. Al-Mehmadi et al - 3 unrelated patients with EIEE47. Patients had diff disease course although all had seizures. Guella et al, 2016 - 15 year old girl with EIEE47 - developed tonic seizures on second day of life. In all the papers above only variant detected is R52H - de novo in each case. In vitro functional studies done by Siekierska et al 2016 - supports pathogenicity.

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
Epileptic encephalopathy, early infantile, 617166

Publications

• 27872899
• 27164707

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.

Created: 14 Nov 2018, 10:52 a.m.

Comment on mode of inheritance: changed MOI from external clinical review and publications

Created: 14 Nov 2018, 10:47 a.m.

Comment on publications: Added publications that support the association with the phenotype and cases, suggested by external reviewer and recent publication Takeguchi R et al., (2018) PMID:29699863 describes two further unrelated cases, 1 Japanese patient diagnosed with early infantile epileptic encephalopathy (EIEE) and another diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). Both patients had an identical heterozygous missense mutation [c.341G>A:p.(Arg114His)] in FGF12, which was identified with whole-exome sequencing. The mutation is identical to previously reported mutations in cases with early onset epileptic encephalopathy.

Created: 14 Nov 2018, 10:43 a.m.

Comment on phenotypes: added phenotype from external review and checked with OMIM and orphanet

Created: 13 Nov 2018, 5:18 p.m.

Green List (high evidence)

Multiple unrelated patients reported, EE phenotype.

Created: 13 Aug 2018, 12:35 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy, early infantile, 47, MIM#617166

Publications

• 27830185, 27872899, 27164707

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