Gardner's syndrome: Formal genetics and statistical analysis of a large Canadian kindred

In a large Canadian kindred 71 members manifested at least one component of the Gardner's syndrome triad. Thirty‐seven manifested polyposis only (including 10 cases of deduced polyposis), ten members manifested soft tissue abnormality only, and one kindred member manifested bone abnormality only. Nineteen kindred members manifested two triad components; 15 had soft tissue abnormality and polyposis, whereas four had polyposis and bone involvement. Four kindred members exhibited the complete triad, while two known to possess the Gardner gene failed to manifest any triad stigmata. 1. Polyposis . Mean age at onset of symptoms in 30 proven cases was 32.2 years, age at polyposis diagnosis in 48 proven cases was 31.4 years, and age at diagnosis of cancer secondary to polyposis in 25 cases was 37.2 years. Fourteen deduced polyposis cases were diagnosed at a mean age of 57.1 years. 2. Hard and soft tissue abnormality . Lack of precise age at onset precluded statistical analysis. The findings described cover the full spectrum of extra‐colonic involvement now associated with Gardner's syndrome. 3. Formal genetics . Males and females were equally affected. The calculated frequency at birth of individuals heterozygous for the Gardner syndrome gene was 1 in 14,025. Kindred members affected with Gardner's syndrome had a relative biological fitness of 82.2 per cent (males 78.9 per cent and females 85.7 per cent). The estimated mutation rate at the Gardner locus was 13 mutations per million loci per generation. In this kindred, the Gardner syndrome gene was 83.9 per cent penetrant. Possible sources of bias entering into the above calculations are discussed.