Medical Issues in Ehlers-Danlos Syndrome/Hypermobility Spectrum Disorders, Autism Spectrum Disorder, and Unaffected Controls

Background: Ehlers-Danlos syndrome (EDS)/hypermobility spectrum disorders (HSD) are believed to be largely collagen-related disorders, which are often accompanied by neurodevelopmental and neuropsychiatric conditions (Baeza-Velasco et al., 2015). In particular, a growing body of literature suggests overlap between EDS/HSD and some cases of autism spectrum disorder (ASD), although to date this relationship is poorly delineated (Casanova et al., 2018; Baeza-Velasco et al., 2015). The possibility that a subset of autism cases are in fact connective tissue disorders is intriguing and it is therefore important to determine to what extent connective tissue impairment (clinical or subclinical) occurs within the autism spectrum.

Objectives: To study clinical similarities between adults with EDS/HSD, ASD, and controls across key symptom areas to determine the extent of phenotypic overlap across these groups.

Methods: We surveyed 702 adults aged 25 years or older with or without EDS/HSD and/or ASD diagnoses on a variety of EDS/HSD-related health topics, including immune, autonomic, and endocrine symptomology; diagnostic clustering within affected families; hypermobility and occurrences of dislocations/subluxations of joints; skin abnormalities (e.g., bruising, scarring, bleeding); and chronic pain and fatigue.

Results: Compared to controls, the autism group reported similar though less severe symptomology than the EDS/HSD group, especially in areas of immune, autonomic, and endocrine dysregulation; skin abnormalities; and chronic pain. The ASD group did not significantly differ from controls in reported rates of generalized hypermobility unless already diagnosed with EDS/HSD. Interestingly, EDS/HSD mothers with autistic children reported more immune symptoms than EDS/HSD mothers without (p = 0.0119). The same trend was found in EDS/HSD mothers with EDS/HSD children (p = 0.0145), suggesting the maternal immune system may play an important role in both these conditions’ etiologies.

Conclusions: These data suggest that EDS/HSD and autism share some clinical, and perhaps etiological, overlap that should be further studied. This work also indicates that mild connective tissue impairment and chronic pain could be under-recognized issues in ASD that warrant further attention.