By: Dr. Fabiano de Abreu Agrela Rodrigues
The coexistence of Ehlers-Danlos Syndrome (EDS) and Autism Spectrum Disorder (ASD) has received increasing attention in contemporary scientific literature. This association is not merely a clinical coincidence, but may reflect a phenomenon of interaction between neurobiological and somatic vulnerabilities, in which the neurotransmitter gamma-aminobutyric acid (GABA) plays a central role in modulating neural excitability, sensory perception, and visceral self-regulation.
In patients with mild forms of EDS, traditionally neglected in syndromic classification systems, a set of symptoms that transcend classic joint hypermobility are observed. Among them, persistent fatigue, diffuse musculoskeletal pain, autonomic dysfunctions, sensory hypersensitivity, and functional gastrointestinal alterations stand out. These manifestations coincide with domains frequently altered in the autistic spectrum, suggesting a functional overlap that deserves in-depth investigation.
From this perspective, EDS may act as an amplifying or revealing factor of subclinical autistic traits. This is not the direct etiology of ASD, but rather the hypothesis that the somatic fragility and neuroautonomic instability associated with EDS disrupt compensatory networks of the central nervous system, bringing to light cognitive and behavioral patterns compatible with the autistic spectrum.
Dysfunction of the GABAergic system represents the possible pathophysiological link between these conditions. In autism, robust literature points to a reduction in GABAergic activity, associated with a predominance of excitatory signals in cortical and subcortical networks, which compromises sensory filtering and emotional self-regulation. In individuals with EDS, alterations in GABA modulation are observed that can range from deficiency to hypersensitivity, depending on the individual genetic and phenotypic profile. Such neurochemical instability facilitates the emergence of neural hyperexcitability and sensory processing disorders.
This dysregulation is not limited to the brain domain. The association between autonomic dysfunction and tissue fragility leads to a range of side effects, such as prolonged anxiety states, chronic gastrointestinal symptoms (such as gastroparesis, reflux and abdominal distension) and physical manifestations such as chronic pain, orthostatic intolerance and incapacitating fatigue. The perpetuation of these conditions establishes a feedback loop between somatic vulnerability and psycho-emotional overload.
The integrated analysis of the current data suggests that patients with EDS, especially in mild and moderate degrees, should be considered as a population at risk for the increased expression of autistic traits. Early identification of these characteristics may favor more effective neuropsychological and clinical interventions, reducing the functional impact of the EDS-ASD combination.
Understanding the relationship between GABA, autonomic instability and the cross-phenotypic expression between EDS and ASD redefines the clinical and investigative approach to these conditions. Instead of rigid diagnostic categories, a systemic, neuroevolutionary and personalized vision is required, capable of recognizing the complexity of individual profiles and proposing therapeutic strategies that respect their biochemical and structural singularities.
