Link between autism and heart defects offers hope for early autism diagnosis

Autism spectrum disorders are complex neurodevelopmental conditions affecting about 1 in 100 children worldwide. Early diagnosis would allow timely intervention to improve the development and quality of life for children with autism. Scientists have identified over 200 genes associated with autism, but predicting the risk of developing autism based on genetic information is not straightforward. Autism can co-occur with congenital heart disease, which affects the structure, growth and function of the heart. Because congenital heart disease can be readily identified in newborns, a congenital heart disease diagnosis could help identify children at higher risk of developing autism earlier. Scientists have been trying to understand why the two conditions, which affect the development of the brain and the heart respectively, occur together. A team of scientists, led by Dr Helen Willsey from University of California, San Francisco, USA, discovered that tiny hair-like structures called cilia, found on the surface of almost every cell, underlie the shared biology of autism and congenital heart disease, taking us a step closer to early prediction of children at risk of developing autism. This study is published in the journal Development on 24 June 2025.

‘Understanding how autism and congenital heart disease intersect biologically has been technically challenging just due to the sheer number of risk genes involved in both disorders,’ said Willsey. Previous evidence had shown that mutations in 361 genes increased the risk of individuals developing either autism, congenital heart disease, or both. The scientists wondered whether genes linked to congenital heart disease that directly affect nerve cells may be genes that also increase the risk of autism. ‘Here, we looked at how these risk genes function in the development of both the brain and heart and contribute to disease,’ said Willsey.

Nia Teerikorpi, who performed most of the experiments in this study, grew immature human nerve cells that had been mutated to lack one of the 361 key genes in the lab and monitored how well the cells grew. She found 45 genes that affected the growth of the nerve cells. Looking more closely, Teerikorpi and the team found that all 45 genes function in tiny hair-like protrusions (cilia) extending from our cells that are involved in movement, sensation and communication between cells. Willsey explained why one gene in this group – taok1 – caught their attention: ‘Patients with mutations in the taok1 gene appear to have a higher risk of developing autism, and we previously identified taok1 as a predicted congenital heart disease risk gene, but we had not yet tested whether it functions in heart development. So, seeing this gene come up again in this work looking at the shared biology of the two conditions motivated us to study it more closely.’

To study the role of taok1 in the heart and brain, the team altered the gene in frog embryos and then monitored their growth and development. They found that cilia could not form properly on cell surfaces, and they observed defects developing in the heart and brain. This suggests that the other 44 genes identified could also be relevant for the development of the brain and heart, contributing to autism and congenital heart disease.

Building on this work, the team is now actively pursuing the extent to which genes involved in cilia overlap with genes associated with autism and congenital heart disease, ‘what we discovered is the tip of the iceberg for the intersection of autism and congenital heart disease,’ said Willsey, ‘Our findings offer the opportunity to prioritize people with genes associated with both conditions for early monitoring and intervention.’

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ADDITIONAL INFORMATION: Dr Helen Willsey is an Assistant Professor at the University of California, San Francisco and an Investigator with the Chan Zuckerberg Biohub – San Francisco.

REFERENCE: Teerikorpi, N., McCluskey, K. E., Bader, E., Lasser, M.C., Wang, S., Nguyen, C. H., Schmidt, J. D., Kostyanovskaya, E., Sun, N., Dea, J., et al. (2025). Ciliary biology intersects autism and congenital heart disease. Development 152, dev204295. doi:10.1242/dev.204295

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