People with multiple hypermobile joints are diagnosed with Generalized Joint Hypermobility (GJH) when asymptomatic, or Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD) when symptomatic (hEDS/HSD, or 'HSD' here). GJH likely affects about 20% of the U.S. population, while HSD affects 0.5-3% of the US population. Although joint hypermobility is the most visible presentation of HSD, it is a systemic connective tissue disorder affecting multiple body systems. Due to frequent health concerns, HSD may contribute to more than 30% of patients in chronic pain, rheumatology, orthopedic and physical therapy clinics. It is still unclear why some people have asymptomatic hypermobility and others develop complex chronic health issues. However, recent research suggests that the transition might be triggered by severe physiological stress, such as viral infection.

HSD is commonly associated with Postural Orthostatic Tachycardia Syndrome (POTS) and Mast Cell Activation Syndrome (MCAS), as well as gastrointestinal (GI) problems. Recent research suggests that persistent inflammation due to MCAS or COVID may trigger HSD symptoms. The correlation between POTS and HSD may be due to effects of HSD on the autonomic nervous system or to inflammation triggering both conditions. It is also unclear whether body awareness and coordination deficits seen in symptomatic HSD are due to the fundamental connective tissue disorder or due to pain and injuries in HSD. This study seeks to determine whether asymptomatic hypermobile individuals (GJH) also have balance and coordination deficits. The current study hopes to identify factors that correlate with a transition from asymptomatic GJH to symptomatic HSD by following a group of Health Science students forward in time. The study will collect baseline health information including relevant diagnoses, symptoms and function. Physical measurements will include standard clinical tests performed by physical therapists: joint hypermobility and instability, standing balance, neck movement control, and heart rate in response to standing from lying down. The study is likely to last for at least 10 years to follow participants over time.

Most hyper mobility-related research is conducted by clinical researchers, who are generally limited to recruiting research subjects from patients who present to their clinics. There are few opportunities for longitudinal studies of asymptomatic or 'healthy' individuals to identify potential triggers prospectively and to compare to people who do not develop symptoms. A health care academic institution provides the ideal environment for a prospective study, somewhat like the 'Nurses Health Study'* that followed a population of nurses throughout their lives.

The study will collect initial data on:

• Current diagnoses related to HSD, MCAS, and POTS (questionnaire)
• Current symptoms associated with HSD, MCAS and POTS (questionnaire)
• Overall quality of life (questionnaire)
• Physical measures for diagnosing joint hypermobility and instability
• Physical screening for POTS
• Physical screening for body awareness, balance and coordination

Objectives and Hypotheses

1. What is the prevalence of HSD, POTS and MCAS in a 'healthy' young adult population?
2. How often are HSD, POTS and MCAS undiagnosed in a 'healthy' young adult population?
3. Are there factors that trigger or precede the development of widespread symptoms in people who have GJH, causing them to develop HSD?
4. What risk factors are associated with increased likelihood that an individual will develop POTS, MCAS, or HSD?
5. Do balance or motor control in the neck differ in asymptomatic joint hypermobility compared to symptomatic hypermobility?
6. If coordination impairments exist in asymptomatic people with hypermobility, does that predict development of HSD?

Questionnaires will be on secure Google Forms accessed through participants' phones or other electronic devices. Participants may pause and return to the questionnaires if they choose. We intend for the questionnaires to require no more than 30 minutes to complete; we may need to eliminate questions from the current list to achieve this.

Physical measurements will be performed only at the initial data collection. These measurements will be performed by licensed physical therapists, who may be assisted by physical therapy graduate students with adequate training to assist in selected data collection. Data collection will take place in Clarkson Hall. Measurements are likely to be performed at 'stations' by various assessors, but any participant who would like to be in a private room for any or all of the assessment may request that. Physical measurements are likely to take about 30 minutes.

Each year, we will follow up by emailing participants asking them to complete questionnaires that will be a subset of the initial set of questions. Questionnaires will again be implemented through secure Google Forms.

Inclusion Criteria: Clarkson University Health Sciences students. -

Exclusion Criteria: Other physical conditions that preclude collecting >25% of physical measurements at initial data collection.

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Health Science graduate students are typically 20-35 years old, though some non-traditional students might be slightly older.

To ensure privacy of health information in a fairly small subject pool.