With so much focus on a woman’s age during pregnancy, it’s easy to overlook how paternal age can affect genetic risk. As opposed to maternal age-related risk for chromosome abnormalities, like Down syndrome, the father’s age can contribute to genetic changes in the smaller compartments of our chromosomes called genes. So, at what age do we consider men to be at increased risk for these genetic changes to occur in their offspring? While there is no clearly accepted definition of “advanced paternal age,” the American College of Medical Genetics (ACMG) confers that this genetic risk gradually increases for fathers beginning at age 40. Some studies have suggested that the risk is 4-5 times greater for fathers aged 45 and above than for their 20-25-year-old counterparts.
Before we talk about the type of genetic changes associated with advanced paternal age we first need to explain the basics. DNA, genes and chromosomes are the building blocks of inheritance. DNA (deoxyribonucleic acid) is a biomolecule that holds the instruction manual for how our bodies are built. A gene is a segment of DNA that is passed down from parents to children and confers a trait to the offspring. Genes are packaged and organized in to units called chromosomes. We typically have 23 pairs of chromosomes for a total of 46 in every cell in our body. One set of 23 chromosomes comes from our mother and the other set of 23 chromosomes comes from our father. The first 22 pairs of chromosomes are considered our numbered chromosomes (autosomes). The last pair of chromosomes, our sex chromosomes, determines whether we will be male or female. Males have an X and Y chromosome and females have two X chromosomes.
Advanced paternal age is associated with an increased risk for new gene mutations; those that arise in the sperm cell at the time of conception. Specifically, these new mutations occur in genes located on our numbered chromosomes and cause autosomal dominant genetic disorders. This means only one mutated gene copy is required for the disorder to manifest itself. Some examples of these autosomal dominant genetic disorders are achondroplasia, neurofibromatosis, Marfan syndrome, Treacher Collins syndrome, Waardenburg syndrome, thanatophoric dysplasia, osteogenesis imperfecta, and Apert syndrome. These disorders range in severity from physical deformities to shortened life expectancy and diminished quality of life.
There is also an increased risk for X-linked genetic disorders (those associated with genes located on the X chromosome) in male offspring of women whose fathers were of advanced paternal age. Some examples of these X-linked genetic disorders are fragile X, hemophilia A (Factor VIII deficiency), hemophilia B (Factor IX deficiency), Duchenne muscular dystrophy, incontinentia pigment), Hunter syndrome, Bruton agammaglobulinemia, and retinitis pigmentosa.
While there is documented evidence of an association between advanced paternal age and increased risk of new gene mutations, there are currently no prenatal screening or diagnostic testing “panels” to identify affected pregnancies. If you are interested in further discussing your reproductive risk based on advanced paternal age, the genetic counselors at Insight Medical Genetics are here to help you better understand your personal reproductive risk.