Early onset or syndromic epilepsy

Gene: FH

I don't know

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

I don't know

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

Green List (high evidence)

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 Green

Created: 14 Nov 2018, 12:44 p.m.

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

Created: 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.

Green List (high evidence)

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