This protocol covers testing for dominant mutations in the fumarate hydratase (FH) gene which are associated with the familial tumour syndrome, hereditary leiomyomatosis renal cell cancer syndrome (HLRCC). This protocol does not cover mutation testing for the recessive metabolic disorder fumarate hydratase deficiency.
1. An individual with clinical features suggestive of HLRCCr:
- a renal cell carcinoma (RCC) which is FH deficient on immunohistochemistry
- multiple cutaneous leiomyomas (at least one histopathologically confirmed) or
- two or more of the following:
- a single cutaneous leiomyoma (histopathologically confirmed)
- multiple symptomatic uterine leiomyomas
- HLRCC-associated RCC*
- a first-degree relative with a clinical feature of HLRCC*. If the two features are two women affected with symptomatic uterine leiomyomas, then another HLRCC feature must also be present to consider HLRCC.
2. An individual with a HLRCC-associated RCC diagnosed before 40 years of age
3. First degree relative of a child with Fumarate Hydratase Deficiency due to biallelic mutations in the FH gene
4. Where a known pathogenic mutation identified in a relative.
Genetic testing is important for good clinical care of individuals who are suspected of having a heritable mutation in this gene.
*HLRCC-associated RCCs are predominantly high-grade with a papillary growth pattern. However, HLRCC-associated RCCs have been described to show tubulopapillary, tubulocystic, tubular, solid and cystic areas and may overlap morphologically with collecting duct carcinomas. One consistent and distinctive feature is large nuclei with prominent orangiophilic or eosinophilic nucleolus surrounded by a clear halo.rr