From the Guidelines
To determine carrier frequency, it is essential to consider the specific genetic condition and population being tested, with the most recent and highest quality study indicating that the risk of autosomal recessive AT in future children is very low, approximately 1 in 800, as stated in the 2025 study by the American College of Medical Genetics and Genomics 1.
Key Considerations
- The risk of having an affected child can be calculated based on the test results, with partner testing being offered, particularly if there is a family history of the condition or consanguinity 1.
- The American College of Medical Genetics and Genomics proposes a tiered definition of carrier screening, with ATM fitting into tier 4, which includes genes that are recommended to not be offered routinely but in specific circumstances 1.
- Funding for partner testing varies across countries, and some healthcare systems do not fund partner testing, such as the National Health Service in England, which only funds partner testing when the carrier frequency of the condition is higher than 1 in 70 in the relevant population 1.
Population-Specific Carrier Frequencies
- Studies have reported carrier frequencies for various genetic conditions in the Ashkenazi Jewish population, including Tay-Sachs disease, Canavan disease, and familial dysautonomia, with carrier frequencies ranging from 1 in 31 to 1 in 41 1.
- The detection rates for these conditions also vary, with some conditions having higher detection rates than others, such as familial dysautonomia, which has a detection rate of 99% 1.
Clinical Implications
- The most critical factor in determining carrier frequency is the specific genetic condition being tested, with the risk of having an affected child being calculated based on the test results and the population being tested 1.
- Clinicians should consider the tiered definition of carrier screening proposed by the American College of Medical Genetics and Genomics and offer partner testing accordingly, taking into account the funding availability and population-specific carrier frequencies 1.
From the Research
Carrier Frequency Overview
- Carrier screening is the practice of testing individuals to identify those at increased risks of having children affected by genetic diseases 2.
- The primary goal of carrier screening is to identify asymptomatic individuals who carry variants associated with genetic diseases, to inform about the risk of having a child with a genetic disease 3.
Types of Carrier Screening
- Carrier screening can be accomplished through different approaches including ethnicity-based screening, pan-ethnic screening, and expanded carrier screening (ECS) 3.
- ECS takes a broad approach by screening for a large number of genetic diseases irrespective of ethnic background, and ideally is performed prior to conception 3.
Importance of Carrier Screening
- Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions 4, 5.
- Carrier screening allows patients to understand their reproductive risks and make informed decisions about their reproductive health 6.
Limitations of Carrier Screening
- There are many important limitations of ECS to consider, ranging from the yield of unexpected information, uncertainty about the phenotype of a particular disease for which an individual is a carrier, and greater downstream costs associated with further testing and genetic counseling 3.
- The research evidence for current international policy recommendations is limited to non-randomised studies 4, 5.