Ehlers-Danlos Syndrome (EDS) and Postural Orthostatic Tachycardia Syndrome (POTS) frequently coexist, creating a complex clinical picture for many patients. EDS is a group of inherited disorders affecting the connective tissue that provides structure and support throughout the body. Postural Orthostatic Tachycardia Syndrome, or POTS, is a form of dysautonomia characterized by an abnormal and sustained increase in heart rate when moving from a lying to a standing position. This significant overlap, with estimates suggesting that up to 80% of individuals with hypermobile EDS also experience POTS, points to a shared biological pathway. The following details the mechanistic chain reaction that begins with a faulty structural protein and ultimately results in the autonomic dysfunction seen in POTS.
Defining the Underlying Issue: Connective Tissue Failure in EDS
The root cause of Ehlers-Danlos Syndrome lies in defective components of the extracellular matrix, the complex scaffolding that supports cells and tissues. The most abundant of these components is collagen, a protein that acts as the body’s “glue,” providing tensile strength and structural integrity to skin, joints, organs, and blood vessel walls. In hypermobile EDS (hEDS), the most common form associated with POTS, the resulting pathology involves impaired collagen structure and function.
The structural defect results in tissue fragility, meaning tissues are inherently weaker and less elastic. This lack of resilience affects the body systemically, particularly impacting the cardiovascular system and the development of POTS. The faulty connective tissue cannot provide the rigid, supportive framework needed for the body’s circulation. This material defect sets the stage for vascular consequences when gravity is introduced.
Structural Consequences: Vascular Instability and Blood Pooling
The primary physical link between EDS and POTS stems from the effect of defective collagen on the blood vessels, particularly the veins. Veins are responsible for returning deoxygenated blood to the heart and rely on surrounding tissue support and their own ability to constrict to fight gravity. In EDS, the weakened connective tissue makes the venous walls hyper-compliant, or abnormally stretchy.
When a person with this defect stands up, gravity pulls blood into the lower extremities and the abdominal area. Because the veins cannot constrict effectively, a significant volume of blood pools below the diaphragm. This venous pooling results in a sudden, dramatic drop in the blood volume returning to the heart, which is called the central blood volume.
The heart and brain perceive this drop in central blood volume as acute hypovolemia, or low blood volume, even if the total blood amount is normal. This deficit means less blood is available to be pumped to the brain, leading to lightheadedness and presyncope. This structural dysfunction is the physical precursor to the neurological response characteristic of POTS.
The Autonomic Nervous System Response and Dysregulation
The body’s immediate countermeasure to blood pooling is a neurological response mediated by the Autonomic Nervous System (ANS). The ANS controls involuntary functions like heart rate and blood pressure, attempting to restore adequate cerebral blood flow. It senses the low central blood volume and activates the sympathetic nervous system, the body’s “fight-or-flight” accelerator.
This activation results in a surge of the stress hormone and neurotransmitter norepinephrine. The intent is to increase heart rate and constrict blood vessels to force blood back toward the upper body. However, in POTS, this response is dysregulated and often excessive, especially in the hyperadrenergic subtype.
The nervous system overreacts to the pooling, leading to an inappropriate and sustained increase in heart rate (tachycardia) when the person stands. Despite the rapid heart rate, the brain does not receive sufficient blood flow because the structural defect in the veins prevents effective vasoconstriction. The excessive tachycardia is therefore a failed, overzealous attempt by the body to compensate for the fundamental mechanical failure caused by the defective connective tissue.
Co-occurring Factors that Complicate the Connection
Beyond the direct vascular pathway, other conditions frequently seen alongside EDS can complicate and exacerbate POTS symptoms. Mast Cell Activation Syndrome (MCAS) is a common co-morbidity, often referred to as part of a “triad” with EDS and POTS. In MCAS, immune cells release inflammatory mediators that affect vascular tone and permeability, potentially worsening venous pooling and subsequent dysautonomia.
Generalized ligament laxity in EDS patients can affect the junction between the skull and the first two vertebrae, a condition called Craniocervical Instability (CCI). CCI can lead to mechanical compression or chronic irritation of the brainstem and upper spinal cord. Since the brainstem is a central hub for autonomic control, this structural instability can directly disrupt neurological signaling and contribute to or worsen the symptoms of dysautonomia and POTS. These co-occurring issues mean the clinical presentation of POTS in a person with EDS is often a combination of multiple complex and interconnected systemic failures.