title: Potential genetic anticipation in hereditary leiomyomatosis-renal cell cancer (HLRCC).
abstract: Hereditary leiomyomatosis-renal cell cancer (HLRCC) is an autosomal dominant disorder characterised by cutaneous leiomyomas, symptomatic uterine leiomyomas and aggressive type II papillary renal cell carcinoma. It is caused by heterozygous mutations in the fumarate hydratase (FH) gene on chromosome 1q43. We present evidence of genetic anticipation in HLRCC syndrome. A comprehensive literature review was performed to determine the potential for genetic anticipation in HLRCC syndrome. The normal random effects model was used to evaluate for genetic anticipation to ensure reduction in bias. A total of 11 FH kindreds with available multi-generational data were identified for analysis. The mean difference in age at diagnosis of RCC between the first and second generation was -18.6 years (95 % CI -26.6 to -10.6, p < 0.001). The mean difference in age at diagnosis of RCC between the first and third generation was -36.2 years (95 % CI -47.0 to -25.4, p < 0.001). No evidence of anticipation for uterine leiomyomas was observed (p = 0.349). We report preliminary evidence of genetic anticipation of RCC in HLRCC syndrome. Additional clinical validation is important to confirm this observation, which may have practical implications on counseling and timing of surveillance initiation. Exploration of the underlying mechanisms of anticipation in HLRCC would be of considerable biological interest.
authors: Department of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors: Mei Hua
authors: MH
authors: Wong
authors: Chuen Seng
authors: CS
authors: Tan
authors: Soo Chin
authors: SC
authors: Lee
authors: Yvonne
authors: Y
authors: Yong
authors: Aik Seng
authors: AS
authors: Ooi
authors: Joanne
authors: J
authors: Ngeow
authors: Min Han
authors: MH
authors: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D020132:Anticipation, Genetic; D005260:Female; D005649:Fumarate Hydratase / Q000235:genetics*; D006801:Humans; D018231:Leiomyomatosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary; D010375:Pedigree; D012878:Skin Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D014594:Uterine Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: D005649:Fumarate Hydratase