Women Carry Higher Genetic Risk for Autism Transmission
Women with autism carry a greater genetic burden than men with autism, and when women transmit autism-related genes to their offspring, the risk to siblings is higher compared to when men transmit these genes. This phenomenon is explained by the "female protective effect" (FPE), which demonstrates that females require a higher threshold of genetic risk to develop autism themselves 1.
Evidence for Higher Female Genetic Load
Females with ASD carry a greater ASD-related genetic load than males with ASD, and clinically unaffected female relatives carry more autism risk factors compared to unaffected male relatives 1. This means that when a woman has autism or carries autism risk genes, she likely harbors more severe or numerous genetic variants than a male counterpart with similar clinical presentation 1.
Transmission Risk to Offspring
Maternal vs. Paternal Transmission Patterns
Siblings of female probands (children with autism) have higher autism symptom scores than siblings of male probands, as demonstrated in large-scale studies of dizygotic twins using standardized autism assessment tools 1.
The recurrence risk for full siblings is 4% if the affected child is a girl and 7% if the affected child is a boy 1. This counterintuitive finding reflects that girls who manifest autism carry more severe genetic risk, which translates to higher transmission rates to subsequent children 1.
Advancing maternal age is independently associated with increased autism risk (mothers 40-49 years vs 20-29 years: RR=1.15), though the effect is somewhat smaller than paternal age effects 2, 3, 4.
The Female Protective Effect Mechanism
The FPE operates through two primary biological mechanisms 1:
Sex chromosome effects: Either the Y chromosome confers risk or a second X chromosome provides protection, supported by increased ASD rates in Turner syndrome (XO) and 47,XYY syndrome 1.
Sex hormone influences: Testosterone levels during fetal brain development correlate with systematizing traits, social impairments, and reduced empathy in children who develop ASD 1.
Clinical Implications for Genetic Counseling
When counseling families where the mother has autism or is a carrier of autism risk variants, clinicians should emphasize the higher recurrence risk compared to paternal transmission 1. The risk of a second child having ASD is approximately 6% on average in population studies, but this increases to 25-35% if a second child already has autism 1.
Gender-Specific Risk Patterns
In families with only one male autistic child, the risk that the next female child will have ASD is close to 10% 1, reflecting the higher genetic threshold females must cross to manifest the disorder 1.
Males are more likely to meet clinical criteria for ASD than females with comparable genetic risk, as demonstrated in individuals with SHANK1 microdeletions where males developed ASD while females with the same mutation showed only anxiety 1.
Common Pitfalls to Avoid
Do not assume equal transmission risk from mothers and fathers - the female protective effect means maternal transmission often involves higher genetic burden 1. Do not overlook that girls presenting with autism likely carry more severe genetic variants, which has implications for family planning and sibling risk assessment 1.