Advanced paternal age
Advanced paternal age: A man who is age 40 years or older at the time of conception. (There is no universally accepted definition of advanced paternal age but this criterion is often used in genetic counseling.)
Advanced paternal age is associated with an increased risk of new mutations in the offspring. This risk for genetic defects does not increase dramatically at age 40, but rather increases linearly with the age of the father. The risk of genetic defects due to new dominant mutations is 4 to 5 times greater for fathers aged 45 and above than for men in their early twenties.
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.
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