Preimplantation Genetic Testing (PGT) is a diagnostic procedure performed on embryos created through in vitro fertilization (IVF). PGT aims to identify genetic abnormalities before an embryo is transferred to the uterus. Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social communication challenges and restricted, repetitive behaviors. As genetic testing technologies advance, the question of whether PGT can screen for typical ASD is frequently asked. This article examines the science of PGT and the complex genetics of ASD to provide an evidence-based answer.
Understanding Preimplantation Genetic Testing
Preimplantation Genetic Testing is conducted on a small sample of cells, typically taken from an embryo at the blastocyst stage. This biopsy allows scientists to analyze the embryo’s DNA for genetic conditions without affecting the inner cell mass that develops into the fetus. PGT is primarily utilized in two established forms, each targeting a different category of genetic error.
One common application is PGT for Aneuploidy (PGT-A), which screens embryos for an incorrect number of chromosomes. PGT-A checks for whole chromosome gains or losses, such as the three copies of chromosome 21 that cause Down syndrome. Identifying embryos with the correct chromosome number is intended to improve IVF success rates and reduce the risk of miscarriage.
The second primary application is PGT for Monogenic disorders (PGT-M), which focuses on specific single-gene defects. This test is used when one or both parents are known carriers of a particular genetic disease, such as Cystic Fibrosis or Huntington’s disease. PGT-M targets a precise, known mutation within the family history. The goal of PGT-M is to prevent the transfer of an embryo affected by that specific inherited condition.
The Genetic Complexity of Autism Spectrum Disorder
Autism Spectrum Disorder is not a single condition but a constellation of neurodevelopmental differences with diverse underlying causes. The genetic contribution to ASD is high, estimated to account for 40% to 80% of an individual’s risk. This risk is distributed across many different types of genetic changes.
The majority of ASD cases are considered polygenic, resulting from the cumulative effect of hundreds, or even thousands, of common genetic variants. Each variant contributes only a tiny amount to the overall risk. This complex genetic architecture means there is no single “autism gene” that can be easily identified or tested for in most individuals.
A smaller subset of ASD cases, approximately 10% to 30%, is linked to rare, high-impact genetic changes. These changes can involve copy number variants (CNVs), which are large deletions or duplications of DNA segments, or single-gene mutations. These high-impact changes often occur de novo, meaning they are new mutations in the child and not inherited from the parents.
Non-genetic factors also play a role in the expression of ASD, interacting with an individual’s genetic susceptibility. Environmental influences, such as prenatal exposure or the mother’s health during pregnancy, contribute to the complexity of the condition. Due to this combination of many small genetic effects and environmental factors, the predictability of ASD remains low.
Current Capabilities of PGT Regarding Autism
Preimplantation Genetic Testing does not screen for or diagnose the typical, polygenic form of Autism Spectrum Disorder. The technology is not designed to calculate the cumulative risk from the thousands of common genetic variants that contribute to the majority of ASD cases. Therefore, PGT cannot determine an embryo’s overall likelihood of developing ASD for most couples.
PGT-M can be utilized in specific, rare circumstances where a known single-gene disorder associated with a high risk of ASD is present in the family. Conditions like Fragile X Syndrome, Tuberous Sclerosis, or certain neurodevelopmental syndromes caused by a single known mutation can be targeted with PGT-M. In these instances, the test screens for the causal syndrome that carries a strong likelihood of an ASD diagnosis, not for “autism” directly.
For example, if parents are carriers for the mutation that causes Fragile X Syndrome, PGT-M can accurately identify which embryos have inherited that specific pathogenic variant. This is a targeted diagnostic test for a specific disease, distinct from a generalized screen for the complex, polygenic condition of ASD. Some specialized PGT panels are beginning to screen for hundreds of rare variants implicated in neurodevelopmental disorders, but this covers only a fraction of the total genetic risk for ASD.
Limitations and Ethical Landscape of Screening for Complex Traits
The primary technical limitation for screening typical ASD using PGT lies in its polygenic nature, requiring a fundamentally different testing approach. This approach involves calculating a Polygenic Risk Score (PRS), which aggregates the effects of thousands of common genetic variants into a single risk estimate. Although PRS is used in research, its application to embryos, often called PGT-P, is currently unreliable and controversial.
The predictive accuracy of PGT-P for complex traits like ASD is significantly lower than for single-gene disorders. This is because the scores only account for the genetic component of risk. Environmental factors, which cannot be tested in an embryo, have a large influence on the final outcome. Furthermore, PRS calculations rely on population data that may not be accurate across all ancestry groups, raising concerns about generalizability.
The clinical implementation of PGT-P for complex conditions is not recommended by major medical and genetics organizations due to these technical limitations and the surrounding ethical debate. Selecting embryos based on risk scores for non-disease traits, such as intelligence or height, or for spectrum conditions, raises profound societal questions. The practice is seen by healthcare professionals as premature, potentially leading to anxiety for parents and creating difficult choices based on incomplete information.