# Ne oldu?

A recent narrative review published in the Journal of Musculoskeletal & Neuronal Interactions investigates the frequent co-occurrence of hypermobile Ehlers-Danlos Syndrome (hEDS) and Autism Spectrum Disorder (ASD). The authors highlight that epidemiological data show a higher-than-expected comorbidity between the two conditions. A key statistic from a cited systematic review and meta-analysis reveals that the prevalence of joint hypermobility in autistic individuals is 22.3%, rising to 31% when clinically assessed. Similarly, the prevalence of Ehlers-Danlos Syndrome or Hypermobility Spectrum Disorder (HSD) in autistic individuals stands at 27.9%, increasing to 39% with clinical assessment. The review notes that this comorbidity is likely underrepresented due to gender-related underdiagnosis, limited clinical awareness, and fragmented healthcare pathways.

# Ayrıntılar

The review examines the conditions from both clinical and molecular perspectives. On the clinical side, the authors point out that both hEDS and ASD share symptom overlap, including sensory sensitivities, gastrointestinal issues, and motor coordination difficulties. The paper emphasizes that the true extent of the co-occurrence is difficult to ascertain, as many cases likely go undiagnosed. On the molecular level, the review shifts focus to potential biological mechanisms. The authors hypothesize that dysregulation of the WNT/β-catenin signaling pathway and matrix metalloproteinase-9 (MMP-9) could serve as a unifying link. WNT/β-catenin is a critical pathway in embryonic development, tissue repair, and synaptic plasticity. MMP-9 is an enzyme involved in extracellular matrix remodeling and has been implicated in both fibroblast phenotypes seen in connective tissue disorders and synaptic pruning in the brain. The authors suggest that shared dysregulation of these pathways might explain why features of connective tissue fragility and neurodevelopmental differences frequently appear together, though they stress that this mechanistic hypothesis is currently speculative and lacks direct clinical validation.

# Neden önemli?

Understanding the potential overlap between hEDS and ASD is important for several reasons. For patients, recognizing that these conditions can co-occur can lead to more comprehensive care plans that address both connective tissue and neurological symptoms. For clinicians, awareness of this comorbidity can improve screening practices, ensuring that patients presenting with one condition are evaluated for the other. From a research perspective, identifying shared biological pathways, such as those involving WNT/β-catenin and MMP-9, could open new avenues for future investigation into the etiology of both disorders. The review serves as a call to action for the medical community to explore these connections more rigorously, rather than treating the conditions in isolation.

# Sırada ne var?

The authors explicitly state that the hypothesis linking WNT/β-catenin and MMP-9 to the comorbidity of hEDS and ASD is speculative. They call for future research to test these mechanistic theories using original experimental or clinical data. Key areas for future study include verifying prevalence rates in independent cohorts, clarifying the role of gender and diagnostic bias in the observed comorbidity, and exploring whether targeting these pathways could lead to novel therapeutic strategies. The research community is encouraged to move beyond narrative observations toward methodologically detailed studies that can provide clearer evidence on the biological underpinnings of this association.