Genetic testing before pregnancy could be useful to discover unknown hereditary diseases and possible risks before conception.
The use of genetic testing is commonly used as a precaution prior to pregnancy; however, in most cases, genetic tests occur once the woman is pregnant. Researchers from the University of Zurich explored the impact of genetic testing on both parents’ genes to analyse possible risks before conception.
In many parts of the US, broad genetic testing is available to prospective parents and in early pregnancy. The screenings indicate recessively inherited genes that are non-gender specific, meaning genes that only affect the baby if both gene copies carry a mutation.
Testing 3,000 hereditary conditions
Anita Rauch, director of medical genetics at the University of Zurich, and her team in Switzerland addressed whether genetic testing is fit for purpose before conception and during pregnancy. They studied the potential positives and faults of expanded carrier screening (ECS).
The team tested sequence data from 700 patients who already had children with neurodevelopmental disorders. More than 3,000 investigated genes can cause intellectual disabilities, developmental disorders, autism, and other conditions.
“In our study, we were able to show that this type of broad genetic testing can detect the risk of the child having a severe developmental disorder in about 44% of cases if the parents are related by blood – for instance as first or second cousins,” said Anita Rauch. In some population groups, this is quite common, for example, in the Middle East or North Africa.
Genetic testing in non-blood-related parents
The genetic test also detected around 5% of couples who were not blood-related but only if all known recessive genes were investigated.
Recommendations in the US suggest that non-consanguineous couples should only be tested for common genes known to have a certain carrier frequency. “Following the US recommendation would more than halve the risk detection rate because rarer genes also play a part here,” explained Rauch.
The children of non-blood-related couples had a significantly higher proportion of developmental disorders caused by non-hereditary de novo mutations, whereas, in blood-related couples, the hereditary defects in children play a distinctly greater role. As a result, the researchers stated that the likelihood of detecting risks by analysing the parents’ genes is limited for non-blood-related couples.
Pathogenic genes
The researchers also found genetic testing could potentially detect problematic gene variants in known pathogenic genes, in particular, missense gene mutations. This is where the genetic blueprint may or may not be altered, and inherited copy-number variants, in which the number of gene copies is incorrect, have been underestimated. Cases that cannot be detected are generally those in which an inherited and a newly acquired genetic defect occur at the same time.
Moreover, it is likely that several thousands of unidentified genes probably cause developmental disorders. For example, in the study, the cause of developmental disorders in the respective children remained unexplained in around 58% of cases.
The study provides vital insight into the impact of carrier screening. Based on the high risk-detection rate for blood-related parents, the researchers believe that genetic screening should be offered to these couples. In all other cases, the benefits and disadvantages should be weighed up case-by-case to avoid unrealistic expectations.
“If a couple is found to be at risk of having children with neurodevelopmental disorders, they will be fully aware and able to decide whether or not to have children together or to consider prenatal or preimplantation diagnostics,” said Rauch.
However, the results also show that the potential risk reduction strongly depends on the selected genes and variant classifications in the test. According to Rauch, there is still potential for improvement in the tests offered currently: “To improve the clinical benefit, all couples that want a broad genetic test should be considered for screening all recessive genes irrespective of the population prevalence of a gene variant. Laboratories should also use reasonable thresholds regarding when a genetic defect is considered pathogenic.”
