What Is the Likelihood of Autism in the Children of Unaffected Siblings?

By Alison Singer

President, Autism Science Foundation

When an autistic person’s brother or sister is thinking about having a baby, it is natural for them to wonder whether their own child might be autistic. Fortunately, the science around recurrence risk is becoming clearer. Research shows that having an autistic aunt or uncle increases the risk of an autism diagnosis, but that likelihood appears to depend on which side of the family the autistic relative is on, whether that relative is a brother or sister, and the sex of the baby.

One of the largest studies to address this question analyzed over 840,000 children in Sweden and was published in 2020. Children whose mothers had a sibling with autism had a 3.05 times increased likelihood of an autism diagnosis than children without that family history. For children whose fathers had a sibling with autism, the likelihood was 2.08 times higher. (footnote 1). At the time, the prevalence of autism in the general population of Sweden was 1.5%. Risk increased to 3-5% when the child had an autistic aunt or uncle. (footnote 2)

More recently, researchers in Denmark examined this question in considerably greater detail. The study included 1.7 million births and examined not only whether a parent had a sibling with autism, but also whether that autistic sibling was a brother or sister and whether the child was male or female.  (footnote 3). As you would expect, the highest risk was in male children. It was 3.3x higher if the father had a sister with autism. Male children whose father had an autistic brother had an approximately 2.5 times higher likelihood of an autism diagnosis. On the mother’s side, male children whose mother had an autistic brother had an approximately 3 times higher likelihood, while female children in that group had an approximately 2.1 times higher likelihood. Some combinations did not have enough data to produce an estimate, particularly in girls who have a lower rate of diagnosis to begin with (footnote 3). These findings suggest that there is no single recurrence likelihood for nieces and nephews. The family tree matters, and the sex of the baby appears to matter as well.

This is consistent with research on younger siblings of autistic children. In the 2024 update from the Baby Siblings Research Consortium, 1,605 infants with an older autistic sibling were followed prospectively. Overall, 20.2% developed autism. Male infants had a 25.3% recurrence rate compared with 13.1% among female infants. The likelihood was also higher when the older autistic sibling was female: 34.7% versus 22.5% when the older sibling was male (footnote 4).  These sibling data are important because they corroborate the idea that both the sex of the baby and the sex of the autistic relative can influence familial recurrence.

There is also a smaller study from Washington University in St. Louis that directly examined this next generation of offspring. Scientists followed 220 children born to 113 mothers who had an autistic sibling. 13.2% of those children had an autism diagnosis (19 of 111 boys and 10 of 109 girls) (footnote 5). While this finding is important because it directly addresses the population we are trying to understand, the sample was very small, and these results should therefore be considered preliminary rather than a definitive estimate.

What all of these studies suggest is that unaffected siblings may carry some of the familial, genetic liability for autism without meeting diagnostic criteria themselves, and that liability can be passed to their children. But we still have enormous gaps in our knowledge. We do not yet know the precise likelihood for every family situation; we cannot assume that findings from siblings of autistic children apply directly to nieces and nephews; and we don’t know how these patterns relate specifically to profound autism since the studies included people diagnosed with broader ASD, not just those with profound autism. 

This is why the Autism Science Foundation’s Next Gen Sibs Project is so important. By prospectively following babies whose parent is an unaffected sibling of an autistic person, we can begin to answer questions that retrospective studies cannot. Does the baby’s sex alter risk? Does the sex of the autistic aunt or uncle matter? Does having more than one autistic relative change the picture, and if so, how? And with more research across different groups and with the help of genetic counselors, can this information eventually or ever be used to provide families with more accurate estimates based on the features in their family and extended family?  

Families deserve answers that are neither falsely reassuring nor unnecessarily frightening. The science tells us that having an autistic aunt or uncle does increase the likelihood of autism, but certainly does not make an autism diagnosis inevitable. Our goal with Next Gen Sibs is to move from broad population estimates to precise, evidence-based information that families can use for family planning.

The family tree is telling us something important; our job is to follow the science carefully enough to understand what it is saying.

References

  • Bai D, Yip BHK, Windham GC, et al. Inherited Risk for Autism Through Maternal and Paternal Lineage. Biological Psychiatry. 2020;88(5):438–445. doi:10.1016/j.biopsych.2020.03.006.
  • https://www.nih.gov/news-events/news-releases/autism-risk-estimated-3-5-children-whose-parents-have-sibling-autism
  • Schendel D, Ejlskov L, Overgaard M, et al. 3-generation family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions associated with autism: An open-source catalog of findings. Autism Research. 2024;17(10):2144–2155. doi:10.1002/aur.3232.
  • Ozonoff S, Young GS, Bradshaw J, et al. Familial Recurrence of Autism: Updates From the Baby Siblings Research Consortium. Pediatrics. 2024;154(2):e2023065297. doi:10.1542/peds.2023-065297.
  • Ozonoff S, Young GS, Bradshaw J, et al. Familial Recurrence of Autism: Updates From the Baby Siblings Research Consortium. Pediatrics. 2024;154(2):e2023065297. doi:10.1542/peds.2023-065297.
  • Marrus N, Turner TN, Forsen E, et al. “Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk.” Journal of Neurodevelopmental Disorders. 2021;13:39. doi:10.1186/s11689-021-09389-8

This holiday weekend always triggers a reincarnation, a resurrection of the vaccine – autism hypothesis.  Many of you have read about the measles epidemics that are hitting many areas of the country.  But besides vaccines, there are other aspects of the immune system that may be linked to autism in some people.  The include family history of autoimmune disorders as well as specific genetic mutations that confer protection against subtypes of ASD.  This week’s ASF podcast will explore these theories and present different ideas on how the immune response is involved in autism, and if it is at all. Listen to the podcast here.

This week’s podcast combines two important post Mother’s Day topics – parents and eating.  Two recent studies have shown the promise of using parent – delivered interventions to help improve food selectivity and food aversions in kids with autism. These two behaviors can be one of the most frustrating and challenging for parents and kids, and can lead to nutritional deficiencies.  These behaviors can range from mild to severe, and previously, only inpatient or outpatient clinic based approaches seemed to have any benefit.  Now it seems that with coaching, encouragement and instruction from trained experts, parents can help their kids eat better foods. Listen to the podcast here.

This podcast is dedicated to siblings of people with autism who are typically developing. They play an important and beneficial role in development of socialization of those with ASD. But sadly, they also have issues of their own, such as a high rate of issues like anxiety and depression. Those siblings may be genetic carries of a specific mutation and not have an autism diagnosis, but have increased risk for schizophrenia and cognitive disability. Finally, just because they are considered “typically developing” doesn’t mean they don’t have challenges with adaptive behavior. However, they have a very special relationship with their brothers and sisters, and the world needs these strong advocates for the community.

aschwartzman-schoolofed

Allyson Schwartzman at her graduation from Hofstra University School of Education.

By Allyson Schwartzman

When I was graduating from elementary school, someone on the yearbook committee asked me, “What do you want to be when you grow up?” I will never forget thinking for a moment and then stating “an autism teacher”. In my yearbook, there is a picture of me and under it says “an autism teacher”. You might be thinking this is a very interesting answer for a young child to give, but I had a good reason behind this answer. My twin brother, Robert, has autism and over our lives, I saw the progress he made with many thanks to his incredible teachers. I thought to myself, I would love to be just like them so I can help other children with autism. As I matured and got older, I realized this autism teacher job I wanted really meant that I wanted to be a special education teacher.

aschwartzman-yearbook

Allyson Schwartzman’s elementary school yearbook photo.

When I started college at Hofstra University, I was accepted into the School of Education. I graduated with my bachelor’s degree in Early Childhood and Childhood Education and eventually got a job as a Universal Pre-Kindergarten Teacher in a public school district on Long Island. I had this job for two years while in graduate school for my Master in Early Childhood Special Education and Intervention program, also at Hofstra University. I always knew I wanted to be a special education teacher, however, I had to decide on the age range of students I would work with. I decided to go down this route for my master’s because I fell in love with working with young children. There are so many developmental milestones that a teacher can help young children with disabilities reach. I love teaching and helping children grow their physical, intellectual, emotional, and social development through different fun and engaging activities. By being an early childhood special educator, I am able to accomplish these goals with a variety of different students.

After many endless nights of working and studying, I was able to accept my first position this year as an early childhood special education teacher in an integrated preschool. I finally accepted my dream job! I took a job in an integrated preschool setting specifically because I believe in the importance of integration and having students with disabilities learn with and from their peers. All children with disabilities need to be placed in the proper learning environment that works for them, and I am excited to work in this environment.

aschwartzman-robert

Collage of photos with Allyson Schwartzman and her twin brother, Robert.

I am so thankful that my brother Robert has influenced me to go down the path of special education. I am so proud of him and the progress he has made. He drives my dedication to this career choice everyday. It was definitely not an easy road getting here, but I cannot wait to make a difference in the lives of all the students I work with! I can now smile every time I look in my elementary school yearbook because I followed my dream. Now, I am living it.

On this week’s podcast, highlights from the Phelan-McDermid Syndrome Foundation 2018 International Family Conference in Dallas, TX. People with Phelan McDermid Syndrome, or PMS, suffer from seizures and intellectual disability, and about 70% have an ASD diagnosis. This syndrome is caused by mutations of the SHANK3 gene, which is present in about 1% of people with autism, making it the most common single genetic influence of ASD. Learn more about the conference here.

By Meghan Miller, PhD

Kids playing with a tablet

More and more, researchers and clinicians are thinking about how advances in technology can be leveraged for interventions for children with autism. Tablets, computers, and video games have become increasingly available to children in their daily lives. At the same time, the American Academy of Pediatrics has put forth clear screen time guidelines for children, and many parents worry about their children spending too much time in front of a screen or with devices.

In the autism field, technology is providing promising avenues for early detection and intervention. For example, a recent study describes the use of mobile technology to screen for autism in young children. Others have developed apps and virtual reality systems through which treatments can be delivered. But what good are advances in technology-based interventions if parents aren’t interested in utilizing them?

Researchers at the UC Davis MIND Institute on the UC Davis Medical Center campus in Sacramento are conducting a study of parental perceptions of use of technology in treatment of impulsivity in 4 to 7-year-olds with autism spectrum disorder. Parents of 4 to 7-year-old children who have been diagnosed with autism spectrum disorder (ASD) can participate. Families can expect to complete of several online questionnaires about: Your family, your opinions about technology in treatment, and your child’s behavior. These questionnaires will take about 10 minutes of your time.

Take our survey: http://bit.ly/autismtechsurvey

Learn more here: https://studypages.com/s/technology-in-treatment-study-364017/

ASF is proud to announce continued support for the Baby Siblings Research Consortium (BSRC), a network of over 33 research sites around the world studying the younger siblings of people with autism. The Baby Sibs database now tracks over 5,000 younger siblings, with and without autism. The database has been used to develop more sophisticated screening and diagnostic approaches, to understand early biological features of ASD even before symptoms develop, and to inform clinicians of early treatment targets. The additional funding will allow researchers to continue submitting information to expand data points so that a deeper understanding of development across the lifespan can be made. ASF support will also allow scientists to collaborate on key issues like early biological testing and searching for biomarkers of ASD.