By: Dr. Fabiano de Abreu Agrela Rodrigues
For decades, Ehlers-Danlos Syndrome (EDS) and Autism Spectrum Disorder (ASD) were treated as completely separate clinical territories. EDS fell under the responsibility of geneticists and rheumatologists; ASD, of psychiatrists and neuropediatricians. The practical result of this fragmentation was that the same person could move between doctors for years without anyone asking the obvious question: do these two diagnoses appear together more frequently than chance would explain?
The answer, according to the accumulated scientific evidence, is yes.
The systematic review with meta-analysis by Baeza-Velasco et al. (2025), published in the journal Autism, analyzed 20 studies that examined the relationship between ASD, joint hypermobility, Hypermobility Spectrum Disorders (HSD), and EDS. Of the 15 studies that examined the association between ASD or autistic traits and joint hypermobility, HSD, or EDS, 12 reported significant results. The overall prevalence of joint hypermobility in autistic individuals was 22.3%, rising to 31% when only studies with clinical assessment were considered, excluding self-report studies. Regarding EDS and HSD specifically, the overall prevalence in autistic samples was 27.9%, but reached 39% when the diagnostic assessment was conducted clinically.
These numbers are not trivial. We are talking about the fact that, in clinical samples, almost four out of ten autistic individuals evaluated meet the criteria for EDS or HSD.
The relationship, however, is not unidirectional. Researchers have found that two clinically heterogeneous spectrum conditions, ASD and Hypermobility Disorders, co-occur more frequently than would be expected by chance, even though they are treated by completely different medical specialties. Casanova et al. (2020), in the Journal of Personalized Medicine, reviewed the neurobiological and genetic mechanisms that bring the two conditions closer together and proposed that EDS/HSD may represent a subtype of autism, given the overlap of comorbidities, familial co-occurrence, and similarities in autonomic and immunological profiles.
From a genetic standpoint, the authors identified 35 genes simultaneously associated with hypermobility and autism. By mapping these genes onto interaction networks, the genetic sets of EDS and autism with hypermobility formed extensive clusters, suggesting substantial interactions between these networks and a potential mechanism for phenotypic overlap.
Neurobiology also points in the same direction. Structural brain differences in individuals with hypermobility have been identified in regions involved in emotional processing, attention, cognitive control of pain and negative emotions, including the bilateral amygdala, the anterior cingulate cortex, and the parietal lobe—areas whose alterations are also described in autism.
There is also a clinical dimension with serious practical consequences: chronic pain. EDS, particularly the hypermobile subtype (hSED), causes musculoskeletal pain, headache, and visceral pain. In autistic individuals, the perception and expression of pain follow atypical patterns, making the identification of comorbidity even more difficult. Patients with ASD who also present with Hypermobility Disorders are treated by different specialties, and the link between the conditions is rarely established in the clinical context, despite the growing body of evidence suggesting co-occurrence above what would be expected by chance. The concrete risk is that pain, already underestimated in autistic individuals due to communication barriers, will remain undiagnosed and untreated when EDS is underlying.
Another factor amplifying the problem is the historical delay in diagnosing SED. The diagnostic delay was estimated at 14 years for half of SED patients, and 28 years for a quarter of them, constituting the largest diagnostic delay among 16 rare diseases evaluated. When this is added to the underdiagnosis of autism in women, who represent the majority of hSED cases, the problem worsens: since hSED is predominantly diagnosed in women, it is likely that autism spectrum conditions are underidentified in this clinical subpopulation, whose presentation profile often differs from that of men and whose ability to socially mask autism is greater.
What the data demand, therefore, is not just more research, although that is necessary. It demands a change in clinical practice. Professionals who care for autistic individuals should include systematic screening for joint hypermobility and signs of connective tissue disease. Similarly, geneticists and rheumatologists who follow patients with EDS should consider evaluation for neurodevelopmental disorders, particularly in women with social and sensory complaints that, until now, have been attributed to chronic pain or fatigue.
Science has already connected the dots. It’s up to clinical practice to do the same.
References
Baeza-Velasco, C., Vergne, J., Poli, M., Kalisch, L., & Calati, R. (2025). Autism in the context of joint hypermobility, hypermobility spectrum disorders, and Ehlers–Danlos syndromes: A systematic review and prevalence meta-analyses. Autism, 29(8), 1939–1958. https://doi.org/10.1177/13623613251328059
Baeza-Velasco, C., Cohen, D., Hamonet, C., Vlamynck, E., Diaz, L., Cravero, C., Cappe, É., & Guinchat, V. (2018). Autism, joint hypermobility-related disorders and pain. Frontiers in Psychiatry, 9. https://doi.org/10.3389/fpsyt.2018.00656
Casanova, M., Baeza-Velasco, C., Buchanan, C.B., & Casanova, M.F. (2020). The relationship between autism and Ehlers-Danlos syndromes/hypermobility spectrum disorders. Journal of Personalized Medicine, 10(4), 260. https://doi.org/10.3390/jpm10040260
Morlino, S., Dordoni, C., Sperduti, I., Clark, C., Piedimonte, C., Fontana, A., Colombi, M., Grammatico, P., Copetti, M., & Castori, M. (2018). Italian validation of the functional difficulties questionnaire (FDQ-9) and its correlation with major determinants of quality of life in adults with hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 180(1), 25–34. https://doi.org/10.1002/ajmg.b.32698
Dr. Fabiano de Abreu Agrela Rodrigues MRSB holds a post-PhD in Neuroscience and is an elected member of Sigma Xi – The Scientific Research Honor Society (more than 200 members of Sigma Xi have received the Nobel Prize), as well as being a member of the Society for Neuroscience in the United States, the Royal Society of Biology and The Royal Society of Medicine in the United Kingdom, the European Society of Human Genetics in Vienna, Austria, and the APA – American Philosophical Association in the United States. He holds a Master’s degree in Psychology and a Bachelor’s degree in History and Biology. He is also a Technologist in Anthropology and Philosophy, with several national and international degrees in Neuroscience and Neuropsychology. Dr. Fabiano is a member of prestigious high IQ societies, including Mensa International, Intertel, ISPE High IQ Society, Triple Nine Society, ISI-Society, and HELLIQ Society High IQ. He is the author of more than 300 scientific studies and 30 books. He is currently a visiting professor at PUCRS in Brazil, UNIFRANZ in Bolivia and Santander in Mexico. He also serves as Director of CPAH – Centro de Pesquisa e Análises Heráclito and is the creator of the GIP project, which estimates IQ through the analysis of genetic intelligence. Dr. Fabiano is also a registered journalist, having his name included in the book of records for achieving four records, one of which is for being the greatest creator of characters in the history of the press.