A retrospective review of 48 individuals, including 12 families, molecularly diagnosed with hereditary leiomyomatosis and renal cell cancer (HLRCC)

AbstractHereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by autosomal dominant germline mutations in the fumarate hydratase (FH) gene and is characterized by cutaneous leiomyomas, uterine leiomyomas and aggressive renal malignancies. We conducted a retrospective chart review to characterize the patients referred to our Regional Genetics Program for assessment of HLRCC from 2004 to mid-2016. Forty-eight of 69 (69.5%) referred individuals were positive for a pathogenic or likely pathogenic variant inFH; they had an average age of 39.1  years. There were 11 differentFH variants among them. As expected, the most sensitive indications for a positive genetic test were papillary  renal cell carcinoma (RCC) at a young age (5/5; 100%) and multiple cutaneous leiomyomas (18/19; 95%). However, only twenty-two of 48 (46%) individuals with a positive molecular test had cutaneous leiomyomas, which is considerably lower than previously reported and supports the likelihood of ascert ainment bias in previous reports. Notably, we have experience with 1 large family in which there were no cutaneous leiomyomas across a large age range. We confirm that multiple cutaneous leiomyomas and papillary RCCs at a young age have a high positive predictive value for a molecular diagnosis of H LRCC, but that cutaneous leiomyomas are less prevalent in HLRCC than previously understood, and therefore the condition is likely to be under-ascertained. Our understanding of the phenotypic spectrum...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research