When Symptomatic Hypermobility Is Mistaken for MS: What Patients Need to Know

Could an unrecognised connective tissue condition be hiding behind a multiple sclerosis diagnosis? Understanding the diagnostic confusion, the consequences for patients and the questions worth asking.

Christina Applegate recently shared that, after five years of living with a multiple sclerosis (MS) diagnosis, her doctor told her she had been misdiagnosed. Her symptoms remain severe, and she continues searching for an explanation.

Her experience raises an important question: what happens when someone spends years living with a diagnosis that turns out to be incorrect?

For people with symptomatic joint hypermobility, there is another question worth asking: Could an MS diagnosis be masking an unrecognised connective tissue condition, such as Ehlers-Danlos syndrome (EDS)?

This concern has been described in the medical literature. In their 2017 paper, Ehlers-Danlos Syndrome: A Diagnostic Trap for the Neurologist, an Iatrogenic Risk for the Patient, Professor Claude Hamonet and colleagues identify MS among the neurological conditions with which EDS can be confused. They describe how patients can undergo years of neurological investigations while their underlying connective tissue condition remains unrecognised. The authors also discuss diagnostic delays exceeding 20 years.

For patients, this can mean years of unexplained symptoms, repeated specialist appointments, medications and investigations before the wider pattern is recognised.

The concern goes beyond overlapping symptoms. An incorrect diagnosis can determine the direction of medical care for years, while the condition responsible for the patient's difficulties remains unidentified.

What is MS, and how is it diagnosed?

Multiple sclerosis is an immune-mediated disease affecting the central nervous system, which includes the brain, spinal cord and optic nerves.

In MS, inflammatory immune activity damages myelin, the protective covering around nerve fibres, and can also injure the nerve fibres themselves. This disrupts communication within the nervous system.

The areas of injury are called lesions. Depending on their location, they can cause visual disturbances, weakness, altered sensation, balance problems, bladder dysfunction and other neurological symptoms.

Neurologists diagnose MS by combining the patient's medical history, neurological examination and MRI findings. They look for evidence of characteristic inflammatory lesions affecting the central nervous system. Spinal fluid tests and other investigations may provide additional information. The McDonald diagnostic criteria, revised in 2024 and published in 2025, guide this assessment.

Understanding what supports an MS diagnosis matters because symptoms such as weakness, fatigue, sensory disturbances and movement difficulties can have different underlying causes.

Research into MS also examines the role of mast cells, immune cells involved in inflammation and communication between immune cells. Mast cells can influence the blood-brain barrier and inflammatory processes associated with demyelination, making them an area of interest for potential therapeutic approaches. For more on this research, see Should Mast Cells Be Considered Therapeutic Targets in Multiple Sclerosis?.

How can EDS be mistaken for MS?

EDS is a group of connective tissue disorders that can affect joints, skin and multiple body systems.

In hypermobile EDS (hEDS), joint hypermobility and instability can occur alongside persistent pain, fatigue, altered proprioception and symptoms affecting several body systems.

People with hypermobility spectrum disorders (HSD) can experience many of the same difficulties.

Hamonet's paper focuses specifically on EDS, while the wider diagnostic concerns are also relevant when considering symptomatic joint hypermobility.

The authors describe neurological-type symptoms in people with EDS, including:

• Movement difficulties and episodes of marked weakness

• Altered sensation and unusual body perceptions

• Balance and coordination problems

• Visual disturbances

• Bladder symptoms

• Significant fatigue and functional limitations

These symptoms can lead to investigations for MS and other neurological diseases.

The diagnostic difficulty arises when neurological symptoms are investigated without recognising the patient's history of joint instability, connective tissue characteristics and other systemic symptoms.

Proprioception: why EDS can resemble a neurological movement disorder

One of the most important points in Hamonet's paper concerns proprioception.

Proprioception is your body's ability to sense where its parts are and how they are moving.

It helps you know where your foot is when walking, how much your knee is bending or where your arm is positioned without having to watch it.

In people with symptomatic joint hypermobility, altered proprioception can affect coordination and movement control. You may notice that you frequently stumble, struggle to judge where a limb is positioned, need to watch certain movements or experience difficulty controlling an unstable joint.

Hamonet and colleagues describe more severe movement disturbances in some patients with EDS, including episodes they call pseudo-paralysis. Some patients reported difficulty initiating movements despite wanting to move. Others described a limb feeling absent or disconnected from their body.

Imagine experiencing an episode in which your leg becomes extremely difficult to control or you suddenly struggle to walk. Such symptoms naturally lead to concern about neurological disease. A neurologist then needs to determine what is producing the difficulty.

A movement problem associated with altered proprioception and joint instability can look similar in everyday life to one caused by central nervous system disease, even though the underlying mechanisms are different.

This is why the neurological examination, investigation results and connective tissue history need to be considered together.

Can MRI abnormalities contribute to misdiagnosis?

MRI is an important part of diagnosing MS, but interpreting the findings requires more than identifying abnormal areas. White matter contains nerve fibres connecting different parts of the nervous system. Changes in white matter can appear on MRI for several reasons, including inflammatory disease, vascular changes and migraine.

In MS, neurologists assess the location, shape and distribution of lesions, together with the patient's symptoms and neurological examination.

Hamonet and colleagues discuss MRI changes described as leukoaraiosis, a term used for certain white matter abnormalities. They identify these findings as a possible source of confusion with MS-related changes.

A 2018 conference abstract, Symptoms of Hypermobility Spectrum Disorder May Mimic Multiple Sclerosis, examined 475 patients with hypermobility. Researchers reported that:

• 44 patients had white matter abnormalities on brain MRI.

• 18 of those 44 patients had previously received an MS diagnosis.

The findings highlight why MRI abnormalities must be interpreted alongside the patient's neurological findings and wider medical history.

An important question for patients is what makes their MRI findings characteristic of MS and how those findings relate to their symptoms.

Why is EDS still missed?

Hamonet and colleagues describe a central problem: EDS can affect several body systems, while healthcare often investigates symptoms according to the specialty involved.

A patient may see a neurologist for movement difficulties, a rheumatologist for joint pain, a gastroenterologist for digestive symptoms and a urologist for bladder problems.

Each symptom may receive attention without the wider connective tissue pattern being recognised. Several persistent misconceptions can make this problem worse.

Myth 1: EDS and symptomatic hypermobility are exceptionally rare

Some types of EDS are genuinely rare. However, the wider population affected by hypermobile EDS and hypermobility spectrum disorders is considerably larger than older assumptions suggested.

Population studies using overlapping diagnostic categories have estimated that approximately 1 in 500 to 1 in 900 people may be affected by conditions now described within the hEDS/HSD spectrum.

The exact prevalence remains difficult to establish because diagnostic classifications have changed and many people remain undiagnosed.

When symptomatic hypermobility is regarded as exceptionally rare, clinicians may overlook it even when the medical history contains relevant signs.

Myth 2: Everyone with EDS has stretchy, velvety skin

One persistent misconception is that EDS can always be recognised by extremely stretchy or unusually velvety skin.

Skin characteristics vary between EDS types and individuals.

Some people have unusually soft skin, increased skin extensibility, easy bruising or characteristic scarring. Others have few obvious skin findings.

Markedly stretchy or velvety skin is not a universal requirement for EDS.

In hEDS, diagnosis involves assessing a combination of joint, systemic, family-history and musculoskeletal features.

Relying on a stereotypical appearance can lead clinicians to overlook patients whose symptoms are predominantly neurological, musculoskeletal or autonomic.

Myth 3: Hypermobility means being flexible

Joint hypermobility and muscle flexibility are different characteristics.

Joint hypermobility refers to movement beyond the expected range at a joint, while joint laxity describes looseness in the structures that help stabilise it.

A person can have lax or unstable joints while experiencing muscle tightness, pain, stiffness and restricted movement.

Joint range of motion can also change with age, injury, pain and reduced activity.

Someone who experienced significant joint hypermobility during childhood may now present with stiffness, persistent pain or limited movement.

This is why historical joint problems, repeated sprains, subluxations, dislocations and joints giving way remain important.

Myth 4: A negative genetic test excludes hEDS

Genetic testing can identify disease-associated variants in several EDS types.

For hypermobile EDS, there is currently no established molecular test that confirms the diagnosis.

Clinicians diagnose hEDS through clinical assessment, medical history and evaluation of relevant alternative conditions.

You can read more about the clinical features and diagnosis in our blog here.

When lifelong symptoms seem normal

Hamonet's paper also highlights an important reason symptoms can be missed.

When you have experienced something since childhood, you may assume everyone experiences it.

Perhaps your joints have always felt unstable. You may have experienced repeated injuries, difficulty sensing where your limbs are positioned or unusual fatigue for as long as you can remember.

You may never have mentioned these experiences during a neurological appointment because they seemed unrelated to your current symptoms.

Yet they may be essential clues. A detailed history can reveal connections between symptoms that were previously investigated separately.

What are the consequences of an incorrect MS diagnosis?

An incorrect diagnosis can affect years of medical decisions. Once MS appears in a patient's medical record, it may influence which treatments are prescribed, how new symptoms are interpreted and which investigations are requested.

The patient may continue receiving care directed towards MS while the underlying condition remains unrecognised.

Unnecessary medication and treatment risks

MS disease-modifying therapies are intended to reduce inflammatory disease activity and help prevent relapses or future neurological damage. Depending on the medication, they can affect immune function and require monitoring for infections, blood abnormalities, liver problems and other complications.

When someone has been incorrectly diagnosed with MS, they may be exposed to treatment risks without receiving the intended benefit of controlling MS disease activity.

In The Contemporary Spectrum of Multiple Sclerosis Misdiagnosis: A Multicenter Study, Solomon and colleagues examined 110 patients whose MS diagnoses were later found to be incorrect. The researchers reported:

• 77 patients (70%) had received disease-modifying therapies.

• 34 patients (31%) experienced unnecessary morbidity associated with misdiagnosis.

• 36 patients (33%) had lived with the incorrect diagnosis for at least ten years.

• 79 patients (72%) had an identifiable earlier opportunity for a correct diagnosis.

These findings show how an incorrect diagnosis can continue influencing care long after the initial assessment. MS misdiagnosis is a recognised clinical problem. A 2024 systematic review and meta-analysis examined published research on MS misdiagnosis and underdiagnosis. Across six studies, the pooled proportion of MS misdiagnosis was approximately 15%, although estimates varied between studies.

Why the connective tissue history matters during treatment

Hamonet and colleagues also discuss potential risks associated with certain investigations and treatments in people with EDS. They raise concerns about lumbar puncture in patients with tissue fragility and corticosteroid treatment in those with reduced bone density.

The individual risks depend on the person's clinical circumstances, but recognising a connective tissue condition provides important information when planning investigations and treatment.

A correct diagnosis helps ensure that treatment addresses the condition responsible for the symptoms and that relevant risks are considered.

If you are concerned about an existing MS diagnosis, a specialist reassessment can review both the evidence supporting the diagnosis and the treatment plan.

What should you tell your neurologist?

If you have an MS diagnosis or are undergoing neurological investigations, consider whether your medical history contains signs of symptomatic joint hypermobility that have not been discussed.

Think about your experiences now and earlier in life.

• Joint history: Have you experienced repeated sprains, subluxations, dislocations or joints giving way?

• Childhood symptoms: Were you described as double-jointed, or did you experience unusual joint movement or instability?

• Proprioception: Do you struggle to sense where your limbs are positioned or need to watch certain movements to control them?

• Pain and fatigue: Have these affected several parts of your body or persisted for many years?

• Other body systems: Have you experienced dizziness, bladder problems, digestive disturbances, allergies, autonomic symptoms or unusual skin and tissue characteristics?

• Family history: Do relatives experience similar joint problems, persistent pain or other multisystem symptoms?

These details can help clinicians recognise a pattern that may have been missed when symptoms were investigated separately.

Seven questions to ask your neurologist

If you have an MS diagnosis alongside a history of symptomatic joint hypermobility, these questions can help you understand the evidence behind your diagnosis.

1. Which clinical findings and investigation results support my MS diagnosis, and how do they meet the diagnostic criteria?

2. What makes the lesions on my MRI characteristic of MS, and how do they relate to my symptoms and neurological examination?

3. Has Ehlers-Danlos syndrome or a hypermobility spectrum disorder been considered as an alternative explanation for my symptoms?

4. Could proprioceptive disturbances, joint instability or peripheral nerve problems explain some of my movement or sensory difficulties?

5. How does my history of joint laxity, instability, persistent pain and symptoms affecting other body systems fit into the diagnosis?

6. If my diagnosis is reassessed, how will my current medication and any further investigations be reviewed?

7. Would a second opinion from an MS specialist, together with an assessment by a clinician familiar with EDS and HSD, help clarify the diagnosis?

You can also explain your concern directly:

"I have a history of joint hypermobility, instability and symptoms affecting several body systems. I have read research describing EDS being mistaken for neurological conditions, including MS. I would like to understand whether my connective tissue history has been considered and which findings support my current diagnosis."

Looking at the whole picture

Christina Applegate's experience illustrates how difficult it can be when a diagnosis that has shaped years of medical care is reconsidered. Her symptoms remain, and the search for an explanation continues.

Hamonet and colleagues describe a specific diagnostic problem in people with EDS: neurological symptoms can lead to investigations and diagnoses, including MS, while the underlying connective tissue condition remains unrecognised.

EDS can remain unrecognised when clinicians overlook its multisystem presentation or rely on outdated misconceptions about what the condition should look like.

When neurological symptoms are interpreted without considering the patient's wider medical history, an incorrect MS diagnosis can have lasting consequences, including unnecessary treatment, delayed recognition of the underlying condition and years of unanswered questions.

Understanding how a diagnosis was established gives patients the knowledge to ask informed questions, bring overlooked symptoms into the discussion and request a more complete assessment.

References and further reading

1. Hamonet C, et al. Ehlers-Danlos Syndrome (EDS): A Diagnostic Trap for the Neurologist, an Iatrogenic Risk for the Patient. EC Neurology. 2017;7(2):46–53.

2. Montalban X, et al. Diagnosis of Multiple Sclerosis: 2024 Revisions of the McDonald Criteria. The Lancet Neurology. 2025.

3. Symptoms of Hypermobility Spectrum Disorder May Mimic Multiple Sclerosis. Neurology. 2018;90(15 Supplement).003.

4. Solomon AJ, et al. The Contemporary Spectrum of Multiple Sclerosis Misdiagnosis: A Multicenter Study. Neurology. 2016;87(13):1393–1399.

5. Zürrer WE, et al. Misdiagnosis and Underdiagnosis of Multiple Sclerosis: A Systematic Review and Meta-analysis. Multiple Sclerosis Journal. 2024.

6. Hypermobile Ehlers-Danlos Syndrome. GeneReviews, NCBI Bookshelf.

7. Should Mast Cells Be Considered Therapeutic Targets in Multiple Sclerosis? 2020.

This article is intended for patient education and supports informed discussions with healthcare professionals. Diagnostic reassessment and changes to prescribed treatment should be planned with the treating medical team.