What This Diagnosis Means for You: hEDS, HSD, and Connective Tissue Disorders

Adapted from Chapter 2 of When Your Body Needs More Care: A Practical Guide to Hypermobility, Connective Tissue Disorders, and Creating a Life That Works by Maggie Buckley, MBA, BCPA. Published by EDS Connective. Download the full eBook free →

A diagnosis rarely arrives with a tidy explanation attached. If you've been told you have hEDS, HSD, or are still being evaluated for a connective tissue disorder, you may be left wondering what that actually means for your body day to day. This post, adapted from Chapter 2 of When Your Body Needs More Care, walks through what connective tissue is, why a single diagnosis can take years to land, and why symptoms that feel scattered across your body are often more connected than they seem.

What This Diagnosis Means for You

A diagnosis does not tell you everything, but it can begin to explain what kind of body you are living in. It can help make sense of why the same demands may feel different for you than they do for someone else, and why your body may need more support, more recovery, or a different way of moving through the world. Learning about connective tissue is not only about anatomy. It is also about recognition: understanding the structure you are working with, where it is resilient, and where it may need more protection. In that way, diagnosis is less a destination than the first clear look at the boat you are learning to navigate—and the waters it has already been carrying you through.

With a calmer view, you can start gathering the knowledge and skills that help you live well with a heritable connective tissue disorder. In this chapter, you will look at what "heritable connective tissue disorder" means, how these diagnoses are made, and why hypermobility can appear across several different conditions. Some people are hypermobile and never become symptomatic. For others, the same trait is part of a broader pattern that affects how the body functions and what kinds of support it needs. In simple terms, an HCTD is a broad label for a group of genetic conditions that affect connective tissue. When connective tissue is altered, it can lead to structural and functional changes throughout the body. One way to picture it is the story of The Three Little Pigs: the houses may look similar from the outside, but the building materials matter, and weaker materials change how the structure holds up.

The phrase "heritable disorder of connective tissue" is often traced back to Victor McKusick's 1955 article, "The Cardiovascular Aspects of Marfan's Syndrome: A Heritable Disorder of Connective Tissue." In 1956, the first edition of McKusick's Heritable Disorders of Connective Tissue discussed conditions including Marfan Syndrome (MFS), Ehlers-Danlos syndrome (EDS), osteogenesis imperfecta (OI), pseudoxanthoma elasticum, and Morquio syndrome. In later editions (including the 2002 version), the connective tissue disorder landscape expanded and was organized to include conditions such as the following:

• Osteogenesis Imperfecta (OI)
• Ehlers-Danlos Syndromes (EDS)
• Marfan Syndrome (MFS) and Microfibrillar Disorders
• Cutis Laxa, Pseudoxanthoma Elasticum, and Homocystinurias
• Menkes Disease and Occipital Horn Syndrome
• Epidermolysis Bullosa (EB)
• Various metabolic, bone, and skin disorders (e.g., Alkaptonuria, Osteopetrosis)

That list—plus Loeys-Dietz syndrome (LDS) and Stickler syndrome—represents some of the differential diagnoses a clinician may consider when you show up with hypermobile joints and related musculoskeletal and skin concerns. I'm sharing this with you for one reason: to help you see why identifying a specific subtype is rarely quick or simple.

What Is Connective Tissue?

When you hear the words "connective tissue," you might immediately think of tendons and ligaments—the bands that connect muscle to bone and help your joints work smoothly. But connective tissue is much bigger than that. It is everywhere: in your bones and muscles, in your skin, and in fascia, the web-like layer under your skin that wraps and supports muscles and other structures.

When you talk about HCTDs, you are talking about conditions you are born with that affect how your body builds connective tissue. One simple way to picture this is that your body's "recipe" for making things like collagen varies. Different conditions can affect different parts of your body, and sometimes more than one at once. To sort out what is going on, your healthcare professional usually combines your symptoms, your medical and family history, and what they can observe on an exam.

That exam may include checking how far your joints move, seeing how your skin stretches and bounces back, and looking for certain eye features. For example, you might have a bluish tint to the whites of your eyes, sometimes called blue sclera. That can be seen in osteogenesis imperfecta, but it can also appear in other connective tissue conditions.

If you're hypermobile, it can feel like you're always trying to find a steady footing—like standing on a moving boat. When a joint moves more than it's built to, your body often recruits different muscles to jump in and "hold things together." Over time, that extra work can add to soreness or pain. You might also deal with subluxations (partial slips) or dislocations.

Connective tissue is one of your body's main support systems. It helps hold structures in place so your muscles and bones can move safely. It cushions your organs, helps protect and insulate you, and connects your skin to the layers underneath so your skin can sit smoothly. Even your blood vessels rely on connective tissue for strength and support.

Collagen is a major building block of connective tissue—often described as your body's "glue." Joint looseness can become more noticeable during childhood and growth spurts, when your body is changing quickly. One way to picture it is this: as your bones get longer, your tendons and ligaments ideally act a bit like rubber bands, taking up slack while everything adjusts. If your connective tissue is stretchier, or if it does not "spring back" in the usual way, your joints can start to feel wobbly or unstable as your muscles catch up to the bones. And because your muscles also contain connective tissue, building and maintaining muscle tone for extra support can take more effort than for someone with more stable connective tissue.

Depending on the specific condition you have, differences in connective tissue can affect how strong, stretchy, or repairable your tissues are. That is one reason symptoms can show up in different parts of your body. You might notice mostly joint issues, or you might also have skin differences, digestive symptoms, or blood-vessel-related concerns.

Irman Forghani, MD, FACMG

Director of Clinical Genetics and Genomics · Chief of RAD Center for Precision Medicine · Mount Sinai Medical Center 

"Connective tissue is the body's structural framework—the material that gives strength, support, and flexibility to nearly every organ system. It is composed of proteins like collagen and elastin, which function like cables and elastic bands, holding tissues together while allowing resilience and movement. But connective tissue is more than scaffolding. It is a dynamic, living environment that surrounds cells, blood vessels, and nerves, enabling communication and coordinating processes such as healing and inflammation.

"Because it is present throughout the body, disruptions in connective tissue can have widespread effects, involving the joints, skin, cardiovascular system, eyes, digestive tract, and nervous system. Symptoms that may seem unrelated are often linked by a shared underlying issue. In heritable connective tissue disorders, genetic changes affecting these structural components or their regulation alter tissue integrity and signaling, leading to the diverse clinical features we observe in practice."

When your joints feel unstable, they may move past their usual safe range. That can contribute to repeated joint slips, subluxations, dislocations, and ongoing pain. Your skin can be part of the picture too. You might notice very soft or stretchy skin, easy bruising, or scars that heal differently, such as thin, papery scars or sunken scars. Stretch marks can also appear even without major weight changes. And because your pelvis supports many organs and tissues, issues such as hernias or prolapse can occur in some connective tissue conditions.

Connective tissue can be hard to "see" in regular medical care because it touches so many parts of your body. Specialists often focus on one system at a time—heart, digestion, joints, feet, or nerves. If connective tissue is the common thread for you, your symptoms can feel scattered, and it can take time to connect the dots and build a care team that looks at the whole picture.

If looseness and instability are part of your life, it can help to focus on support and control rather than flexibility. Many people begin with physical therapy, not just for injury, but to learn safer joint mechanics, alignment, and how to move within a more controlled range. Occupational therapy can help you solve day-to-day problems, such as finding braces, splints, and tools that make tasks easier on your joints.

For exercise, many people do best with a gentle, steady approach that builds strength slowly over time. Options can include swimming, resistance bands, modified yoga or Pilates, and carefully progressed strength training. This is where the "start low, go slow" rule matters: your body often responds better to gradual, repeatable progress than to pushing hard and paying for it later.

You might use braces for certain activities to reduce strain, and regular movement breaks can be easier on your body than staying in one position for too long. You may also hear about proprioception, which is your body's sense of where it is in space. Practicing neutral positions while lying down, sitting, standing, and moving between positions can help improve that awareness. Posture work is usually a full-body project—head and shoulders, ribs, hips, knees, ankles, and feet. The goal is to learn what "neutral" feels like in your body without locking or over-straightening your joints, and from there to build the kind of functional strength that makes your joints feel more supported.

Day-to-day symptom management is often a mix of strategies: hydration, nutrition, pacing, and working with allied health professionals, such as physical therapists, occupational therapists, and registered dietitians or nutritionists, to address pain and function. You might try an anti-inflammatory eating style or follow a specific plan, such as a Mediterranean-style approach, while aiming for enough variety to support overall health and address nutritional deficiencies. If you are considering supplements or new routines, it is worth checking with a clinician or pharmacist first—especially if you take other medications or have other health conditions.

As you understand more about connective tissue and the role it plays in your body, it becomes easier to put words to the different kinds of discomfort you might feel. Joint pain may come from repeated strain or joints moving more than they should. Muscle pain can come from muscles working overtime to stabilize you, sometimes staying tight for long periods. Nerve-related pain can happen when nearby nerves become irritated. Skin discomfort may be related to bruising or the way your skin heals. When you can describe these patterns clearly, it becomes easier to explain what you are experiencing and to work with your care team to determine what supports you best.

Here is a more technical way to describe what you have been reading so far—without losing the main point. Connective tissue is the material that supports, protects, and gives structure to many other tissues and organs throughout your body. There are many kinds of connective tissue, but most consist of relatively few cells plus an extracellular matrix, the material outside the cells. That matrix is usually composed of collagen fibers, elastic fibers, proteoglycans, and non-fibrous material collectively called the "ground substance."

When people talk about connective tissue, they are often referring to structures such as tendons, ligaments, fascia, and dura, the tissue that surrounds and protects your central nervous system. Connective tissue also includes bone and cartilage. Collagen is the most abundant protein in your body and one of the main proteins in connective tissue. It gives tissue much of its strength, flexibility, and resilience. There are many types of collagen, and many of the Ehlers-Danlos syndromes involve changes in what are called fibrillar collagens.

Collagen also matters for proprioception, which is your body's sense of where it is in space. The connective tissue around your joints plays a major role in helping you detect where a limb is, how it is moving, and how your body is positioned relative to the world around you. When connective tissue is lax because of collagen differences, proprioception may be less reliable. That can show up as poor coordination or a feeling of clumsiness. You might bump into walls or door frames, struggle more on stairs, or have a harder time navigating uneven ground because it is harder to tell exactly where your body needs to land.

If your body does not make enough collagen, or if the collagen is structurally different, poorly organized, or unable to assemble into fibrils in the usual way, connective tissue can lose some of its mechanical integrity. In practical terms, your tendons and ligaments may not do their jobs as effectively. Because collagen's role is largely structural, changes in collagen can reduce tensile strength, which may contribute to joint instability, subluxations, and dislocations. Collagen also helps maintain your skin's strength and elasticity. When collagen structure is altered, and the collagen fibrils in the skin are disorganized, this can contribute to the hyperextensibility seen in some HCTDs, as well as to skin fragility, such as skin that tears more easily or heals in unusual ways.

How Connective Tissue Diagnoses Happen

Getting a connective tissue–related diagnosis can feel both clarifying and incomplete, especially when your symptoms involve more than one body system. A label such as Joint Hypermobility Syndrome may accurately describe loose joints, pain, partial slips, or full dislocations that affect function. But it can still miss the bigger picture if your other symptoms and body systems were not fully considered at the time. Even so, diagnosis matters. It can connect you to information, resources, and the right kinds of clinicians. It can guide what symptoms need monitoring or treatment, highlight medication, anesthesia, or surgical issues that affect safety, and point you toward strategies that might otherwise be overlooked.

If you are still waiting for a diagnosis, it is reasonable to care for your body as though any of the HCTDs could still be possible. In practical terms, that means focusing on stability, strength, and safer movement while also paying attention to patterns that may suggest common co-occurring conditions, such as dysautonomia, mast cell activation, or cardiovascular concerns.

Lara Bloom

President & CEO, The Ehlers-Danlos Society · Academic Affiliate Professor of Practice in Patient Engagement and Global Collaboration, Penn State College of Medicine

"Many face years—sometimes decades—without a diagnosis, navigating a system that overlooks or misunderstands their symptoms. Even with a diagnosis, access to knowledgeable healthcare professionals and coordinated multidisciplinary care remains limited in most parts of the world."

It also helps to know that diagnostic best practices change over time. For example, someone diagnosed with Ehlers-Danlos syndrome, Hypermobility Type in 2001 under the 1997 Villefranche Nosology—which described six EDS types—might later be reclassified as having hypermobile Ehlers-Danlos syndrome under the 2017 criteria. Another person with overlapping features might have been diagnosed with EDS Type III in 1993, only to be later reclassified into a type of Loeys-Dietz syndrome or another connective tissue disorder as research sharpens the distinctions between conditions and genetic testing becomes more accessible. In other words, a diagnosis can change not because your symptoms were imagined, but because science, diagnostic tools, and classification systems keep evolving. See Appendix A for a fuller history of how Ehlers-Danlos syndrome subtypes have changed over time.

It can also help to picture what is happening on your clinician's side of the table. To reach a diagnosis, they review your medical history, examine your body, study prior records, and compare your symptoms and physical findings against the criteria for many possible conditions. In some cases, that means narrowing the list from dozens—or even hundreds—of possibilities.

Genetic testing can be very helpful, but it works best when combined with your medical history, a careful clinical exam, and a detailed review of your records. It also has real limits. Test panels vary from one laboratory to another. Not all disease-causing variants are known yet. A result may identify a variant of uncertain significance, which means a change was found in the DNA, but researchers do not yet know whether it is actually linked to disease. Testing ordered without a proper medical evaluation is less reliable, and interpretation is most accurate when performed by someone with specialized genetics training.

Irman Forghani, MD, FACMG

Director of Clinical Genetics and Genomics · Chief of RAD Center for Precision Medicine · Mount Sinai Medical Center 

"Diagnosing a connective tissue disorder is like assembling a puzzle—no single feature tells the whole story. It requires integrating a detailed personal and family history, careful physical examination, and often, genetic testing to identify the underlying cause. A comprehensive evaluation is essential because many of these conditions share overlapping, multisystem, and nonspecific features. A complete workup, including genetic testing, helps to confirm a diagnosis and distinguish between look-alike conditions with different risks and management implications.

"Genetic testing plays a central role, particularly when the presentation suggests a recognizable syndrome. But the goal is not simply to assign a label—it is to guide surveillance, inform treatment decisions, clarify recurrence risk, and help patients and families better understand the road ahead."

One reason genetic interpretation can be frustrating is that the reference range is still incomplete. Not everyone in the world has had their genome sequenced, and most people who have undergone testing are of European ancestry. That means the comparison data is uneven. When a rare variant is found, researchers may need more information from relatives or from people with similar ancestry to better understand what that change means. As more people participate in testing and research, the reference base grows, and future interpretations become stronger.

When your results come back, variants may be labeled pathogenic, likely pathogenic, or of uncertain significance. Those findings are then weighed alongside your symptoms, family history, and exam findings. Much of this work is based on educated guesses. Your data are compared with what is currently known, and patterns in the research are used to estimate which symptoms may appear and how much they may affect function. As the science improves, interpretation can too.

A practical question you may eventually ask is whether the right genetic test or panel was chosen in the first place. Hypermobility by itself can point to more than 200 different conditions, and not all of them are HCTDs, such as the Ehlers-Danlos syndromes, Loeys-Dietz syndromes, Marfan syndrome, osteogenesis imperfecta, or Stickler syndrome. Your clinician uses your records, history, and exam to narrow that list, often focusing on features such as family history, vascular signs, skin findings, skeletal characteristics, eye findings, and hearing-related features.

Historically, research and diagnostic protocols focused most heavily on conditions associated with life-threatening vascular problems or visible structural differences, largely because they were the most urgent to identify. One benefit of that focus is that it gradually produced better descriptions of subtypes and a clearer picture of the wider range of symptoms people with HCTDs can experience. Each new study, each refinement of diagnostic criteria, and each improvement in testing gives clinicians more tools to confirm or rule out conditions that fit your history, symptoms, family pattern, and exam findings. That process can feel slow on the patient's side, but over time, it makes diagnosis more accurate and care more targeted.

Co-occurring Conditions

Because collagen is found throughout the body, it is common for more than one body system to be involved in a heritable connective tissue disorder. That is one reason you may hear people use shorthand phrases such as "EDS plus the Trifecta." At first, that phrase can be confusing. In practice, it grew out of patient experience: people noticed certain patterns showing up together, compared notes, and then brought those observations back to clinicians and researchers.

Alan Hakim, MD, MA, FRCP(UK)

Medicine & Rheumatology · Hypermobility-Related Disorders · Principal Investigator Registry & Biobank, The Ehlers-Danlos Society

"If you ask a general doctor on the street what EDS is, you're more likely to get 'I don't know.' But if they do know, they'll probably say it's something about joints and something about skin. Well, it's an awful lot more than that—ocular, dental, neurological, gastrointestinal, pulmonary, cardiovascular, musculoskeletal, bladder. Every single system is involved."

Originally, the "Trifecta" usually referred to three commonly discussed conditions: dysautonomia, mast cell activation syndrome (MCAS), and EDS. As clinicians and researchers looked more intentionally beyond the core joint, skin, and vascular findings that were emphasized in earlier descriptions of HCTDs, they began to recognize more overlapping conditions and symptom patterns that warrant additional scrutiny and research. Over time, the conversation widened.

Many of these conditions overlap, which is one reason the overall picture can feel confusing. For example, chronic pain may show up alongside dysautonomia, MCAS, sleep disorders, neurological issues, or gastrointestinal problems. Sleep problems may also be linked to chronic pain, dysautonomia, neurological symptoms, or GI symptoms. In real life, these systems often affect each other rather than staying neatly separate.

Research is still ongoing to understand how often these conditions occur in people with different types of HCTDs and which combinations tend to cluster together most often under which type or subtype diagnosis. What matters most for you, though, is what you are actually experiencing. This list is not a checklist of expected features, and it does not mean you will develop every condition on it. It is also not a reason to rush toward invasive testing or treatment without careful evaluation. Just as diagnosing an HCTD can take time, diagnosing co-occurring conditions may also take time and may involve several specialists. To protect your energy and mental health, focus first on the symptoms you have now. Then decide which ones most need evaluation, with the practical goal of finding symptom management that helps you live as fully and steadily as possible. You do not need to read the whole horizon at once; you only need the next clear marker in the water. One of the conditions people often hear about early is mast cell activation syndrome, or MCAS.

Mast Cell Activation Syndrome (MCAS)

MCAS is one of the co-occurring conditions that people with hypermobility, heritable connective tissue disorders, and a range of other chronic conditions may hear about early on. While it frequently appears alongside HCTDs, it is not exclusive to them—MCAS occurs across many diagnoses and is increasingly recognized as part of a broader pattern of immune dysregulation. Mast cells are part of the immune system. They help the body respond to infection, allergens, and injury by releasing chemicals such as histamine and tryptase. When that release happens too strongly or at the wrong time, it can lead to symptoms such as flushing, itching, hives, swelling, stomach pain, diarrhea, congestion, dizziness, rapid heart rate, or, in some cases, anaphylaxis. Because mast cells are present in many tissues, symptoms can involve more than one body system at once.

Diagnosis can be frustrating because MCAS is not confirmed by one simple test. Doctors usually look for repeated episodes affecting more than one body system, improvement with medicines that target mast cell mediators, and laboratory evidence of mast cell activation collected during or near a flare. Timing matters, and normal results between flares do not always settle the question. Treatment usually focuses on reducing triggers when possible, using medicines such as antihistamines and other mast cell–targeted therapies, and having an emergency plan in place if severe reactions are a risk. The practical goal is to notice patterns, document what happens, and work with a knowledgeable clinician to sort out what is contributing to your symptoms.

Dysautonomia

Dysautonomia is a broad term for conditions that affect the autonomic nervous system, which controls automatic functions such as heart rate, blood pressure, sweating, digestion, temperature regulation, and the body's response to standing upright. It is one of the co-occurring conditions that people with hypermobility, heritable connective tissue disorders, Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), migraine, autoimmune illness, diabetes, and other chronic conditions may hear about early on. One common pattern is orthostatic intolerance, which means symptoms happen or worsen when a person is standing or sitting upright and often improve when lying down. Symptoms can include dizziness, lightheadedness, shakiness, fatigue, nausea, feeling overheated, a racing heart, headaches, brain fog, stomach problems, exercise intolerance, trouble standing for long periods, and fainting or near-fainting. Because the autonomic nervous system affects many body systems at once, symptoms can feel wide-ranging and difficult to connect at first.

POTS is one type of dysautonomia, but it is not the same as dysautonomia as a whole. In simple terms, all POTS is dysautonomia, but not all dysautonomia is POTS. Diagnosis can take time because symptoms often overlap with many other conditions and may change depending on hydration, illness, hormones, heat, activity, or recovery from infection. Doctors often start by listening closely to symptom patterns and checking heart rate and blood pressure while lying down and standing, and some people may need additional autonomic testing. Treatment depends on the person, but may include fluids, salt when appropriate, compression garments, pacing, activity changes, and medication. The practical goal is to notice patterns, document what happens, and work with a knowledgeable clinician to better understand what is driving your symptoms and build a treatment plan that feels realistic and supportive.

As a diagnosis like this begins to make more sense, the picture often becomes both clearer and more complex. You may start to see how connective tissue, the nervous system, the immune system, pain, sleep, digestion, and daily function affect one another in ways that were not obvious before. That does not mean you need to solve everything at once. It means you can begin to notice patterns, name what is happening more clearly, and decide what needs attention first. And once a diagnosis starts to make more sense in the body, it often changes how it feels in the heart and mind as well. That is where we turn next.

Keep reading: Building a System That Supports You: Appointment Prep for hEDS and HSD →

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