Advanced Paternal Age (APA): Yes, it’s a Real Thing, and Here’s What It Means

By Nicholas Paolino — October 29, 2015

1 min read

Last time, we discussed the significance of Advanced Maternal Age (AMA) and the measures your doctor and genetic counselor will take to ensure a healthy pregnancy for both you and your child. If you recall, AMA is most directly associated with an increasing risk for chromosome abnormalities, such as Down syndrome. Well, it’s not just women who can impose increased risks for genetic and developmental issues on their children based on advancing age. Men aged 40 or older at the time of conception can also contribute to the increased risk of new gene mutations in their children by being of Advanced Paternal Age (APA).

Because sperm divide continuously throughout a man’s life, the new mutation rate in sperm cells is much higher than in a woman’s egg cells. Think of cranking out a product in a factory on a conveyor belt (such as the iconic chocolate factory scene from the classic comedy masterpiece, “I Love Lucy”). As a product is created over and over again, mistakes are bound to be made and missed and to accumulate as the assembly line grows older and more tired (no offense, dads).

Unlike with AMA, there is no evidence to suggest a significant increase in the risk for fetal aneuploidy due to Advanced Paternal Age. APA does, however, appear to be associated with a modest increase in the risk of

  • Miscarriages
  • Extra or missing pieces of chromosome material (duplications/deletions) in children
  • New mutations following autosomal dominant inheritance that can cause disease with just a single mutation in a gene set (new mutation rate of 0.3-0.5%)
  • Spontaneous mutations on the X chromosome that are passed on to a man’s daughter, potentially causing disease in her children
  • Schizophrenia, autism spectrum disorder, and childhood cancers

The autosomal dominant conditions most strongly associated with Advanced Paternal Age are those caused by mutations in the genes FGFR2, FGFR3, and RET. Mutations in these genes can cause significant skeletal conditions such as Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, achondroplasia, and thanatophoric dysplasia or cancer predisposition syndromes such as MEN2A and MEN2B.

At this time, there is no prenatal testing that can target these conditions. Additionally, given that in the context of APA these are conditions associated with a new mutation in a child (not inherited), no carrier screening is available prior to conception to assess these risks. Ultrasound –specifically a fetal anatomy survey at 18 to 20 weeks of gestation– is useful to assess general growth and physical development of the baby, this can be used to screen for birth defects associated with some of the previously mentioned disorders. However, older men can be reassured that the risk to their offspring is low overall for these issues.

In closing, we all have issues with growing older, but those issues are not the same for men and women when it comes to reproductive risks. Although APA is a far less common indication for a genetic counseling referral in comparison to other issues (Advanced Maternal Age, family history of a condition, etc.), that by no means makes it less important. A genetic counselor will still be able to explain the associated risks, discuss screening options, and (hopefully) help alleviate some stress.