Genetic disease in the offspring of older fathers

Autosomal dominant genetic diseases may result from the transmission of a trait by a carrier parent or from gene mutation in one of the gametes from which the child develops. The mean age of fathers of affected persons has been found to be greater than expected for several autosomal dominant diseases due to new mutations. To assess the clinical importance of this observation, the relative and absolute frequencies of offspring with autosomal dominant diseases due to mutation in the sperm from fathers of various ages have been calculated. The relative frequency of new autosomal dominant mutations in children increases logarithmically with paternal age during the usual years of fatherhood. The absolute frequency of autosomal dominant disease due to new mutations among the offspring of fathers who are 40 years of age or older is estimated to be at least 0.3 to 0.5%. This risk is many times greater than that for children of young fathers and is similar in magnitude to the risk of Down syndrome among the offspring of 35- to 40-year-old mothers. Thus, it is good public health policy to recommend that both men and women complete their family a before age 40, if possible.