Early onset or syndromic epilepsy
Gene: FGF12
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
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
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 publicationsCreated: 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 orphanetCreated: 13 Nov 2018, 5:18 p.m.
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
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to FGF12.
Source NHS GMS was added to FGF12.
Zornitza Stark: Multiple unrelated patients re
Gene: fgf12 has been classified as Green List (High Evidence).
Gene: fgf12 has been classified as Green List (High Evidence).
Mode of inheritance for gene: FGF12 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGF12 were set to
Phenotypes for gene: FGF12 were changed from to Epileptic encephalopathy, early infantile, 47, 617166
Expert Review Amber was added to FGF12. Panel: Genetic Epilepsy Syndromes
FGF12 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
FGF12 was created by Sarah Leigh