Genetic Epilepsy

Gene: FH

Green List (high evidence)

Well established gene-disease associations. Loss of function is the mechanism of disease. Monoallelic variants associated with decreased fumarate hydratase enzyme activity cause FH tumour predisposition syndrome (also known as HLRCC; PMID: 11865300, 28300276, 20301430). FH deficiency (also known as fumarase deficiency or fumaric aciduria) caused by biallelic variants results in severe neonatal and early infantile encephalopathy (PMID: 8200987, 20549362, 31746132, 20301679). FH encodes for both mitochondrial and cytosolic FH enzyme isoforms, which catalyze hydration of fumarate to malate.

Created: 10 May 2022, 4:31 a.m. | Last Modified: 10 May 2022, 5:09 a.m.

Panel Version: 0.14031

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
hereditary leiomyomatosis and renal cell cancer MONDO:0007888; fumaric aciduria MONDO:0011730

Publications

• 11865300
• 28300276
• 20301430
• 8200987
• 20549362
• 31746132
• 20301679

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

Green List (high evidence)

Seizures are a well documented feature of this disorder, which results in severe neonatal and early infantile encephalopathy 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: 22 Jan 2020, 10:11 a.m. | Last Modified: 22 Jan 2020, 10:11 a.m.

Panel Version: 0.277

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fumarase deficiency, MIM#606812

Publications

• 20301679
• 10805328
• 20549362
• 15221078
• 16151915