Paternal Age Increasing Genetic Disorders in Offspring

There are two types of paternal age effects. One relates to the autosomes and the other to the X chromosome. New autosomalmutations for dominant conditions show up in the children. Their diseases are due directly to advanced paternal age.

New mutations on the X chromosome are usually not evident in the children. They are transmitted to daughters who are at risk for having sons with X-linked diseases. This is an indirect paternal age effect; it is the effect of the age of the maternal grandfather.

Examples of autosomal dominant conditions associated with advanced paternal age include achondroplasia, neurofibromatosis, Marfan syndrome, Treacher Collins syndrome, Waardenburg syndrome, thanatophoric dysplasia, osteogenesis imperfecta, and Apert syndrome.

Examples of X-linked conditions associated with increased maternal grandfather's age include fragile X, hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), Duchenne muscular dystrophy, incontinentia pigmenti, Hunter syndrome, Bruton-type agammaglobulinemia, and retinitis pigmentosa.