New research sheds light on the relationship between parental age and congenital disorders. - Video

While it's been known that advanced paternal age increases the likelihood of offspring with conditions like bone and heart malformations (e.g., Achondroplasia, Apert, or Noonan syndrome) as well as neurodevelopmental disorders such as schizophrenia and autism, recent research suggests that while certain pathogenic mutations correlate with paternal age, others do not. Moreover, some mutations may arise in the father's testis before sexual maturity.

Delayed fatherhood heightens the risk of new mutations causing congenital disorders in children. Fibroblast growth factor receptor 3 (FGFR3) is a human protein found in tissues like cartilage, the brain, intestines, and kidneys. Driver mutations, more prevalent in older men's sperm, significantly elevate the risk of congenital disorders.

For the study, researchers collected sperm samples from anonymous donors, aged 23 to 59, and examined the variant frequency for genetic mutations in ten different FGFR3 variants.

They discovered that the FGFR3 variant linked to Achondroplasia, the most prevalent form of short-limbed dwarfism, increases with paternal age. Similarly, another variant associated with Thanatophoric dysplasia, a severe skeletal disorder in children, also showed an increase with advancing paternal age.

However, many other FGFR3 variants were found to have no correlation with paternal age.

“Young dads also face a higher risk of having kids with pathogenic mutations, said the paper’s lead author, Irene Tiemann-Boege.

Reference: Genome Biology and Evolution; DOI: 10.1093/gbe/evae015