Complete Penetrance and Absence of Intrafamilial Variability in a Large Family with Hereditary Leiomyomatosis and Renal Cell Carcinoma.

BACKGROUND

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant familial disorder due to FH mutation. Despite a considerable increase in information about the genetic background, inter- and intrafamilial phenotypic variability/penetrance are not well documented.

OBJECTIVE

To describe a large French HLRCC family and provide new data on penetrance and intrafamilial variability.

MATERIALS AND

METHODS

The whole family was contacted for clinical examination, skin biopsy, uterine and kidney imagery and molecular analysis.

RESULTS

The family included 22 members in 3 generations. The second generation consisted of 13 members who were older than the expected age of onset of disease manifestations. Of the 12 available members of this second generation, 6 (1 man and 5 women, aged 44-57 years) had a novel FH mutation. All had the same mild phenotype with cutaneous asymptomatic leiomyomas, uterine fibroids (if women) and no kidney tumor. The other 6 members not bearing the familial mutation had normal clinical and radiological findings. In this second generation, the penetrance was therefore complete, and there was no intrafamilial variability in the clinical expression of the mutation.

CONCLUSION

This study provides additional data on genotype/phenotype correlation, intrafamilial variability and penetrance that should help to improve prognosis and genetic counseling.