Are children of older fathers at risk for genetic disorders?

Abstract

Genetic risks related to paternal age should be of interest to clinical andrologists counselling older men who wish to father a child. Theoretically, the number of (pre-meiotic) mitotic cell divisions during spermatogenesis and their remarkable increase with ageing compared with oogenesis would be in favour of genetic risks for the offspring of older men. But for numerical and structural chromosomal anomalies, such an influence of paternal age has not been found. However, in several autosomal dominant disorders affecting three specific genes (fibroblast growth factor receptor 2 and 3, RET proto-oncogene) the risk for a child to be affected increases with paternal age at time of birth. For other autosomal dominant -X chromosomal dominant or recessive disorders, the available data are sufficient to support the concept of a positive relationship between paternal age and de novo gene mutations. Studies analysing gene sequences of affected children and their parents would allow further evaluation of this topic. The impact of paternal age on disorders with a complex genetic background, however, is a matter of debate. A significant effect of paternal age could not be shown for nonfamilial Alzheimer's disease, congenital heart defects, nonfamilial schizophrenia, acute lymphoblastic leukaemia or prostate cancer.