Hereditary Leiomyomatosis and Renal Cell Cancer
HLRCC/FH tumour predisposition syndrome (OMIM#150800, ORPHA:523) is reported in more than 300 families and is likely to be an under-recognized genetic disorder. Prevalence is unknown, older estimates suggest 1:200.000 individuals.
Affected individuals are at an increased risk of developing the following benign and malign tumours:
HLRCC/FH tumour predisposition syndrome is caused by a germline heterozygous pathogenic variant in the fumarate hydratase gene (FH).
HLRCC/FH tumour predisposition syndrome is inherited in an autosomal dominant manner, meaning that each child of an affected individual has a 50% chance to inherit the familial FH likely pathogenic/pathogenic variant and is at risk of developing disease. Preimplantation and prenatal genetic testing are possible if the pathogenic variant has been identified.
Germline pathogenic variants in both copies of FH gene lead to fumarate hydratase deficiency, an autosomal recessive syndrome. Affected children have a short lifespan and a severe neurologic impairment (OMIM#606812, ORPHA:606812). This should be considered in genetic counselling.
Individuals at risk should have periodic dermatological and gynaecological evaluation. Yearly renal MRI should be performed from an early age (8-10 years).