The term “Asperger’s” is no longer a distinct medical diagnosis, having been incorporated into the broader category of Autism Spectrum Disorder (ASD) in 2013 (DSM-5). ASD is a complex neurodevelopmental condition characterized by persistent challenges in social interaction, communication, and restricted or repetitive patterns of behavior. ASD is considered a polygenic condition, meaning it involves the combined influence of many different genes, rather than a single gene. The question of whether ASD is inherited from the mother or the father requires examining the specific genetic mechanisms that contribute to this complex disorder.
Understanding ASD Heritability
Autism Spectrum Disorder has a strong genetic basis, with heritability estimates often placed in the range of 80% to 90% based on twin studies. This high heritability confirms that genetic factors are the dominant influence on the risk of developing the condition. However, this does not mean that ASD follows a simple Mendelian inheritance pattern.
The genetic architecture of ASD is highly complex and involves hundreds of genes, each contributing a small part to the overall risk. This is known as a polygenic model, where the risk is accumulated through the interaction of multiple common genetic variants inherited from both parents. The disorder’s complexity arises because these inherited common variants often interact with environmental factors and spontaneous genetic changes.
Specific Roles of Maternal and Paternal Genetics
The inheritance of ASD-related risk factors involves contributions from both parents, but research has highlighted some distinct roles for maternal and paternal genetics. Males are diagnosed with ASD approximately four times more often than females. This observation has led to the hypothesis of a “female protective effect,” suggesting that females may require a higher genetic load of risk variants to present with the condition.
In some cases, X-linked genes, which are passed to sons from the mother, can play a role in neurodevelopmental conditions. However, for the majority of ASD cases, the influence of inherited genes appears to show a subtle paternal bias. Studies of families with multiple affected children have observed that siblings with ASD tend to share a greater proportion of genetic material from their father than their mother.
The father’s age at conception is another well-established factor that significantly influences the risk of ASD. As men age, the process of sperm production involves continuous cell division, which increases the opportunity for new, random genetic mutations to occur. This phenomenon, known as the advanced paternal age effect, leads to an increased risk of de novo mutations being passed to the child.
Mutations That Are Not Inherited
While much of the genetic risk for ASD is inherited, a significant portion of cases, especially in families with no prior history of the disorder, are linked to de novo mutations. A de novo mutation is a spontaneous genetic change that appears for the first time in the affected individual and is not present in the genetic makeup of either parent. These new mutations can occur randomly in the egg or sperm cells before conception or shortly after fertilization.
These non-inherited genetic changes are often highly impactful, sometimes disrupting genes that are crucial for brain development. In families with only one affected child (simplex families), de novo mutations are estimated to contribute to a substantial portion of the cases, potentially ranging from 30% to over 50%.
In contrast, in families with multiple affected individuals (multiplex families), the contribution of de novo mutations is much lower, often around 9% to 11%. This difference underscores that inherited genetic factors are the primary cause in families with a strong history of ASD. The advanced paternal age effect is closely tied to these spontaneous changes.
Calculating Recurrence Risk
Recurrence risk refers to the probability that a couple’s subsequent child will also be diagnosed with ASD. For the general population, the risk of having a child with ASD is relatively low, around 1% to 2%. However, once one child has received an ASD diagnosis, the risk for a younger sibling increases significantly.
Studies on younger siblings of a child with ASD report the recurrence risk to be in the range of 10% to 25%. This risk is higher for male siblings (approximately 25%) compared to female siblings (13%). If the first child’s ASD is caused by a spontaneous de novo mutation, the risk for a subsequent child is generally lower, close to the risk of the general population.
Conversely, if the ASD is due to inherited genetic factors passed down from one or both parents, the risk for future children is at the higher end of the recurrence range. Genetic counseling is an important resource for families, providing personalized risk assessments based on the family’s specific history and genetic testing results. Understanding the mechanisms of inheritance helps families make informed decisions.