Familial atypical multiple mole-melanoma (FAMMM) syndrome: Segregation analysis

Abstract

Genetic analysis was performed on four kindreds with clinical and pathological verification of the FAMMM syndrome. There were 80 affected or at risk members in these families. A segregation ratio of 0.47 was observed, which is consistent with an autosomal dominant mode of inheritance. Three obligate gene carriers who lacked any FAMMM phenotypic manifestations were observed and the rate of penetrance for the FAMMM gene was calculated to be 0.93. Cancer at all anatomical sites (exclusive of cutaneous malignant melanoma and intraocular malignant melanoma) showed a five-fold increase (p <0.004) in risk for gene carriers when age corrected and compared to the population expectation. Although there was an apparent excess of carcinoma of the lung, pancreas, and breast, the number of family members studied with specific organ cancer was too small; therefore, a larger sample size will be needed to verify this apparent excess. Our findings warrant further investigation in additional FAMMM kindreds.