Early onset or syndromic epilepsy
Gene: FH
As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.Created: 25 Nov 2019, 8:50 p.m. | Last Modified: 25 Nov 2019, 8:50 p.m.
Panel Version: 1.440
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
AR Fumarase deficiency. AD variants associated with Leiomyomatis and renal cell cancer. Several cases on HGMD Pro - however would testing be problematic as it would identify people who may be at risk of cancer?Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Fumarase deficiency, 606812; Leiomyomatosis and renal cell cancer, 150800
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, 12:58 p.m.
From GeneReview PMID: 20301679. Fumarate hydratase deficiency results in severe neonatal and early infantile encephalopathy that is characterized by poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Epileptic seizures are common (40%-80%), although age of onset and seizure type are variable (PMID:10805328, PMID:20549362). Infantile spasms (epileptic spasms) accompanied by hypsarrhythmia on EEG have been reported (PMID:15221078, PMID:16151915).Created: 14 Nov 2018, 12:56 p.m.
Comment on publications: Added publications to support upgrading of the gene to GreenCreated: 14 Nov 2018, 12:44 p.m.
Comment on mode of inheritance: Added MOI from external clinical review and publicationsCreated: 14 Nov 2018, 12:36 p.m.
Comment on phenotypes: Added phenotype suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel.Created: 14 Nov 2018, 12:36 p.m.
Seizures are a feature of this metabolic disorder.Created: 13 Aug 2018, 12:42 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Fumarase deficiency, MIM#606812
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: FH were changed from Fumarase deficiency, 606812; Seizures to Fumarase deficiency, OMIM:606812
Gene: fh has been classified as Amber List (Moderate Evidence).
Source Wessex and West Midlands GLH was added to FH.
Source NHS GMS was added to FH.
Zornitza Stark: Seizures are a feature of this
Gene: fh has been classified as Green List (High Evidence).
Gene: fh has been classified as Green List (High Evidence).
Publications for gene: FH were set to 2314594; 10805328; 10805328; 20301679
Publications for gene: FH were set to
Mode of inheritance for gene: FH was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FH were changed from to Fumarase deficiency, 606812; Seizures
Expert Review Amber was added to FH. Panel: Genetic Epilepsy Syndromes
FH was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
FH was created by Sarah Leigh