What is the link between Autism and Ehlers-Danlos Syndrome?

Recent research continues to highlight the relationship between Ehlers-Danlos Syndrome (EDS), particularly the hypermobile type (hEDS), and Autism Spectrum Disorder (ASD). This connection is not only compelling but offers new perspectives on how these two conditions may share genetic, neurological, and sensory processing pathways. By understanding this overlap, we can improve diagnosis, treatment, and support strategies for individuals managing both conditions.

The Connection Between EDS and ASD

Hypermobile EDS (hEDS) is a connective tissue disorder characterized by joint hypermobility, chronic pain, and systemic complications. Increasing research suggests that individuals with hEDS are more likely to be diagnosed with neurodevelopmental disorders, including ASD. For example, studies have found that up to 6% of children with hEDS or Hypermobility Spectrum Disorders (HSD) have ASD, compared to the general population​​. This significant overlap indicates that the connective tissue abnormalities in EDS might also affect neurological development, particularly in areas responsible for motor coordination, proprioception, and sensory processing.

How Genetics and Neurology Influence the EDS-ASD Link

Both ASD and hEDS have genetic underpinnings. In the case of hEDS, a genetic cause has not yet been definitively identified, but abnormalities in collagen production are known to affect connective tissue integrity, leading to joint laxity, chronic pain, and other symptoms. On the neurological side, this collagen dysfunction may also play a role in brain development. Motor issues, such as clumsiness and coordination difficulties, are common in both ASD and hEDS​. Studies show that individuals with hypermobility often exhibit differences in brain structures related to proprioception (the body’s ability to sense its movements and position) and motor control​. These differences may account for the motor delays often seen in both populations.

The Role of Sensory Processing in the EDS-ASD Overlap

Sensory processing difficulties are a hallmark of ASD and are also commonly seen in individuals with hEDS. The heightened sensitivity to stimuli such as light, sound, or touch is more than just a behavioral issue— it can reflect underlying neurological processing differences. Sensory overload is common in both ASD and hEDS, and may be exacerbated by the physical discomfort caused by joint hypermobility, muscle fatigue, and chronic pain​.

Mast Cell Activation Syndrome (MCAS) and the Gut-Brain Axis

Mast Cell Activation Syndrome (MCAS) is another condition frequently linked to both ASD and EDS, further complicating the clinical picture. MCAS involves the abnormal release of histamines and other inflammatory mediators from mast cells, causing widespread symptoms such as gastrointestinal disturbances, chronic inflammation, and allergic reactions​​.

In ASD, gastrointestinal (GI) problems are particularly prevalent, with symptoms like constipation, diarrhea, and food sensitivities being common. These issues are believed to be tied to the gut-brain axis, a network of communication between the gut and the central nervous system. Disruption in this axis, particularly through inflammatory processes like those seen in MCAS, may lead to neuroinflammation, further exacerbating behavioral and cognitive symptoms in individuals with ASD​. MCAS-related inflammation may worsen sensory sensitivities, fatigue, and anxiety, making the management of both ASD and hEDS more complex.

Autonomic Dysfunction and EDS-ASD

Autonomic dysfunction is another common feature in both hEDS and ASD. Individuals with hEDS often suffer from Postural Orthostatic Tachycardia Syndrome (POTS), a form of dysautonomia characterized by abnormal heart rate and blood pressure regulation, leading to dizziness, fatigue, and fainting. Research has shown that individuals with ASD also exhibit signs of autonomic dysregulation, including gastrointestinal dysmotility, abnormal sweating, and difficulty regulating body temperature​​. This overlap suggests that autonomic nervous system dysfunction could be a shared pathway between these two conditions.

Mitochondrial Dysfunction: A Shared Pathway

Another potential link between ASD and hEDS is mitochondrial dysfunction, which has been found in both conditions. Mitochondria are responsible for energy production within cells, and when their function is impaired, it can result in fatigue, cognitive difficulties, and developmental delays—symptoms often seen in individuals with both ASD and hEDS​​. Mitochondrial dysfunction may also contribute to the chronic pain and energy deficits experienced by many individuals with hEDS, further complicating their overall management.

Diagnosing and Managing the EDS-ASD Overlap

One of the significant challenges in diagnosing individuals with both EDS and ASD is the overlapping symptoms. Chronic pain, fatigue, and sensory processing difficulties are common to both conditions, often leading to misdiagnosis or delayed diagnosis​​. Autistic individuals, for instance, may struggle to express their pain or discomfort clearly, and clinicians might overlook physical symptoms in favor of focusing on behavioral or developmental concerns.

Accurate diagnosis is essential for accessing appropriate treatments and support. Early intervention strategies, including physical therapy, sensory integration therapy, and pain management techniques, can significantly improve quality of life for individuals managing both conditions. Physiotherapy, tailored to the individual's needs, can help strengthen muscles and stabilize hypermobile joints, reducing pain and preventing injuries​.

Assistive devices, such as braces or orthotics, may also be recommended to provide additional joint support. However, it’s crucial to take a multidisciplinary approach, involving not just rheumatologists and geneticists, but also occupational therapists, psychologists, and gastroenterologists to address the full spectrum of symptoms​.

Conclusion: A Need for Holistic, Multidisciplinary Care

The overlap between Autism Spectrum Disorder and Ehlers-Danlos Syndrome highlights the need for comprehensive, multidisciplinary care. With shared pathways such as immune dysregulation, mitochondrial dysfunction, and sensory processing difficulties, managing both conditions requires a tailored, holistic approach. By recognizing the commonalities between ASD and hEDS, healthcare providers can better support individuals and their families, offering a more integrated approach to treatment that addresses both the physical and neurological aspects of these conditions.

Future research will continue to shed light on the genetic and biological underpinnings of these overlapping conditions, offering hope for more targeted treatments and interventions in the future.

References (MLA)

• Cederlöf, M., et al. “Nationwide Population-Based Cohort Study of Psychiatric Disorders in Individuals with Ehlers-Danlos Syndrome or Hypermobility Syndrome and Their Siblings.” BMC Psychiatry, vol. 16, 2016, pp. 207. https://doi.org/10.1186/s12888-016-0922-6.
• Kindgren, E., Perez, A. Q., and Knez, R. "Prevalence of ADHD and Autism Spectrum Disorder in Children with Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome: A Retrospective Study." Neuropsychiatric Disease and Treatment, vol. 17, 2021, pp. 379–388. https://doi.org/10.2147/NDT.S290494.
• Shetreat-Klein, M., Shinnar, S., and Rapin, I. "Abnormalities of Joint Mobility and Gait in Children with Autism Spectrum Disorders." Brain and Development, vol. 36, no. 2, 2014, pp. 91–96. https://doi.org/10.1016/j.braindev.2012.02.005.
• Delhey, L. M., Tippett, M., Rose, S., et al. "Comparison of Treatment for Metabolic Disorders Associated with Autism: Reanalysis of Three Clinical Trials." Frontiers in Neuroscience, vol. 12, 2018, https://doi.org/10.3389/fnins.2018.00019.
• Tofts, L. J., et al. “Pediatric Joint Hypermobility: A Diagnostic Framework and Narrative Review.” Orphanet Journal of Rare Diseases, vol. 18, 2023, https://doi.org/10.1186/s13023-023-02717-2.

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