Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by differences in social communication and interaction, alongside restricted or repetitive patterns of behavior. The question of how a child can receive an ASD diagnosis when neither parent has one is common. The answer lies in the complex, multifactorial nature of ASD, which involves intricate genetic mechanisms and the subtle expression of traits that may not meet the full diagnostic criteria in adults. Understanding this requires looking beyond simple inheritance to the cumulative effects of many genes, spontaneous genetic changes, and environmental influences.
The Spectrum of Traits in Undiagnosed Parents
It is possible that parents carry genetic risk factors or exhibit mild autistic traits that were never formally diagnosed. Many adults, particularly those in older generations, may have developed effective coping mechanisms or “camouflaging” techniques that mask their underlying traits, making a formal diagnosis difficult to obtain. A parent may possess a high load of autism-linked genetic variants without meeting the full diagnostic threshold for ASD themselves. These subtle, subclinical traits might manifest as differences in social style, intense special interests, or a strong preference for routine. The genetic factors are inherited, but their observable expression, or phenotype, can vary significantly between generations.
How Polygenic Inheritance Works
The most common genetic explanation for ASD in families without a clear history is polygenic inheritance, where hundreds of common genetic variants combine to influence risk. Each variant contributes only a very small amount of risk individually, but their cumulative effect determines the overall genetic susceptibility to the condition. This is often described using the “liability threshold model.”
Every individual inherits a unique set of these common risk variants from both parents, creating a personal “genetic load.” If a child inherits enough of these low-risk variants from both parents, their total genetic load may push them past a specific diagnostic threshold. Neither parent may have passed this threshold on their own, but the combination of their genetic contributions in the child results in the manifestation of ASD. The combined genetic risk for ASD is quantified using a measure called a Polygenic Risk Score (PRS), which sums the effects of many common variants across the genome. Parents can have a moderate PRS, meaning they carry enough variants to contribute risk but not enough to develop the condition themselves. When two such parents have a child, the child has a higher probability of inheriting a substantially greater total PRS that crosses the threshold for diagnosis. Studies estimate that common polygenic variation, which is inherited, accounts for at least 20% of ASD liability.
De Novo Genetic Mutations
Another major mechanism that explains ASD in families with no history of the condition involves de novo genetic mutations. The term de novo refers to a genetic change that appears for the first time in the affected individual, meaning it is present in the child’s DNA but absent in the DNA of both parents. These mutations occur spontaneously in the egg or sperm cell prior to conception, or in the very early stages of embryonic development.
De novo mutations are significant because they often carry a much higher individual risk effect than the common polygenic variants. A single de novo mutation can disrupt a critical gene involved in brain development, leading directly to a substantial increase in ASD risk. These spontaneous changes are thought to contribute to a significant portion of ASD cases in families where only one child is affected, often called “simplex” families. In these low-risk families, de novo mutations may contribute to over half of the ASD cases, compared to a much smaller percentage in families with multiple affected members. The occurrence of these spontaneous mutations is not directly related to the parents’ existing genetic load for ASD. The risk of these mutations also increases with advanced paternal age, as genetic changes accumulate in sperm cells over time.
Environmental Modifiers of Risk
Beyond genetics, non-genetic factors can interact with an existing genetic predisposition to influence the likelihood of an ASD diagnosis. These environmental modifiers are factors that can trigger or exacerbate an underlying genetic vulnerability. Advanced parental age, particularly paternal age over 35, is a well-established modifier.
Additionally, certain prenatal and perinatal factors can influence risk, such as maternal infections during pregnancy or complications during birth that involve oxygen deprivation. These environmental influences are thought to interact with the child’s genetic landscape, which is already set by inherited variants and de novo mutations. For instance, a child with a moderate inherited genetic load might only cross the diagnostic threshold if a prenatal environmental stressor is present. This gene-environment interaction highlights that ASD often arises from a combination of multiple factors rather than a single cause.