Research
CTC provides research grants to qualified researchers working to better understand our complex conditions, and develop accurate diagnostic protocols and effective new treatments.
The CTC's Research Grant Program advances the field of connective tissue disease research and related disorders. We provide funding to promising researchers who are dedicated to finding breakthroughs for Ehlers-Danlos Syndrome, Loeys-Dietz Syndrome, Marfan Syndrome, or commonly related disorders (ex: Tethered Cord Syndrome, Mast Cell Activation Syndrome).
​
This program aims to:
​
-
Foster new and expanded research in the field of connective tissue diseases
-
Encourage early-career researchers to pursue research on connective tissue disorders and related conditions.
-
Provide seed funding with the potential to secure larger grants in the future
​
More information about our grant requirements and how to apply coming soon!
CTC Funded Research Highlight
The Norris Lab at MUSC
The CTC is proud to offer continued support for the Norris Lab's groundbreaking research to better understand Hypermobile Ehlers-Danlos Syndrome, including their Global Survey Initiative, and studies investigating the role of immune system dysfunction in hEDS. MUSC's findings help close the gap between hEDS patients' lived experiences and the medical and scientific fields' understanding of the condition. Taken together, their research lays the groundwork for improved diagnostic tools and better treatment that addresses the complex, multisystemic nature of hEDS.
About the Global Survey
​Defining the Chronic Complexities of hEDS and HSD: A Global Survey of Diagnostic Challenges, Life-Long Comorbidities, and Unmet Needs
​
The findings, published in 2025, shed light on the complexity of these conditions and the need for updated diagnostic criteria. Read the full publication here.
​
Between September 2023 and March 2024, researchers at MUSC ran a global survey asking people with hypermobile Ehlers-Danlos Syndrome (hEDS) or Hypermobility Spectrum Disorder (HSD) questions about their symptoms, related conditions, healthcare experiences, and quality of life. Over 9,000 people responded to the comprehensive 418-item questionnaire. Out of these responses, the researchers identified 3,906 people who met the strict inclusion criteria.​
Key Findings:
​
Diagnosis is painfully slow. Participants with hEDS reported waiting an average of 22 years from the time their symptoms began to the time they received their diagnosis; participants with HSD reported waiting an average of 17.5 years.
​
The burden of illness is enormous. It affects nearly every body system, not just joints. People with hEDS reported an average of 24 co-occurring conditions, and people with HSD reported an average of 17 conditions. Nearly everyone (98.8%) reported chronic pain, and most spend 5+ hours a week just coordinating medical care, seeing an average of 6+ specialists a year.
​
Current diagnostic criteria needs an update. A review of all survey responses revealed that a quarter of people diagnosed with hEDS didn't actually meet the 2017 criteria, while half of those diagnosed with HSD did meet hEDS criteria. These findings suggest the current diagnostic line between the two may not reflect real biological differences.
​
Figure 4. Burden and distribution of co-occurring conditions in survey participants. (A) Distribution of co-occurring conditions per participant, with group averages of 24 (hEDS) and 17 (HSD). (B) Percentage of participants reporting symptoms across eight major organ system categories.(Daylor et al. 2025).
Hypermobile EDS and the KLK15 Discovery
​
Hypermobile EDS (hEDS) is the most common EDS subtype, but unlike the 12 rare subtypes — which have known genetic markers and testing — hEDS's genetic cause has remained unknown.
MUSC's Norris Lab has identified a promising lead, backed by mouse model evidence.
Important caveat: this research is still limited in scope. It is not a definitive genetic test, and no reliable genetic test for hEDS currently exists.
​
About the Study​
Hypermobile EDS is marked by widespread pain, POTS/dysautonomia, GI issues, and MCAS — symptoms spanning far more than the joints and skin. This pattern led researchers to the kallikrein (KLK) genes: 15 genes that affect connective tissue, inflammation, mast cells, and the autonomic nervous system — systems that map directly onto hEDS's symptom profile.
​​
Why it matters: hEDS may not be just a collagen structure problem — it may also involve faulty protein-cutting enzymes and immune dysregulation. This fits the multisystem symptoms (autonomic, GI, immune) seen in people with hEDS, offering a more complete explanation than collagen defects alone.
Key Findings:
​
Researchers tested 200 hEDS patients. About a third (67 people) had at least one rare change in a KLK gene.
They also found one specific change (variant) in the KLK15 gene that showed up in two families — people with hEDS had it, people without hEDS didn't.
​
Mice engineered with this KLK15 variant developed matching problems: weaker, more elastic Achilles tendons with thinner collagen fibers, heart valve degeneration, and disrupted immune signaling.
​
Graphical abstract. Gensemer, et al. (2025).
Center for the Developing Brain & Spine at Brown Neurosurgery Tethered Cord Syndrome (TCS) Research Program
The CTC is proud to fund critical research to better understand tethered cord syndrome (TCS) and occult tethered cord syndrome (OTCS). ​Led by Dr. Petra Klinge, the TCS Research Program is focused on advancing diagnostics and surgical treatments for people with tethered cord syndrome. The program also aims to develop a better understanding of this complex condition and its association with connective tissue disorders.​​
Currently, areas of focus within the Research Program include:
​
-
Establishing standardized tools for establishing the clinical diagnosis of TCS
-
Monitoring and describing the outcomes of TCS surgery across a large and diverse patient population, as well as defining optimal surgical techniques for improving symptoms and minimizing the risk of complications.
-
Understanding the lived experience of patients with TCS, including identifying the most important patient-reported outcome measures (PROMs) for this disease, and improving how clinicians ask patients about eir symptoms.
-
Understanding the underlying pathophysiology of TCS, including how the abnormal filum leads to symptoms of back pain, neurological findings in the legs, and urinary dysfunction through chronic stress and inflammation of the lower spinal cord.
-
Understanding how connective tissue disorder comorbidities, such as EDS, can contribute to TCS pathology, and better identifying EDS-TCS as an under-recognized phenotype of this disorder.
​​​​​​About Tethered Cord Syndrome
​
Tethered Cord Syndrome is a rare neurological condition that impacts people with hEDS at a higher rate than the general population. Dr. Klinge and her team are looking into the interconnection between TCS and hEDS.
​
A healthy spinal cord can move freely inside the spinal canal to accommodate everyday movements. In TCS, the spinal cord is abnormally attached (tethered) to surrounding tissue, which restricts its movement within the spinal canal. This causes a range of symptoms, including lower back pain, balance problems, leg weakness, numbness, and bladder or bowel issues. If left untreated, TCS can progress to the point where people lose the ability to walk.
​​
Sources
​​
Daylor, V., Griggs, M., Weintraub, A., Byrd, R., Petrucci, T., Huff, M., Byerly, K., Fenner, R., Severance, S., Griggs, C., Sharma, A., Atwal, P., Kautz, S. A., Shapiro, S., Youkhana, K., Lavallee, M., Wilkerson, A., Nichols, M., Snyder, A., Eichinger, J. K., ... Norris, R. A. (2025). Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs. Journal of Clinical Medicine, 14(16), 5636. https://doi.org/10.3390/jcm14165636
​
Gensemer, C., Daylor, V., Nix, J., Norris, R. A., & Patel, S. (2024). Co-occurrence of tethered cord syndrome and cervical spine instability in hypermobile Ehlers-Danlos syndrome. Frontiers in neurology, 15, 1441866. https://doi.org/10.3389/fneur.2024.1441866
​
Gensemer, C., Petrucci, T., Beck, T., Daylor, V., Griggs, M., Griggs, C., Weintraub, A., Byerly, K., Guo, L., Morningstar, J., Kornblau, I., Biggs, R., Moore, K., Koren, N., Hastings, C., Oberlies, E., Zientara, E. R., Devey, E., Dooley, S., Stayer, K., … Norris, R. A. (2025). KLK15 alters connective tissues in hypermobile Ehlers-Danlos syndrome. iScience, 28(9), 113343. https://doi.org/10.1016/j.isci.2025.113343
​
Klinge, P. M., Leary, O. P., Allen, P. A., Svokos, K., Sullivan, P., Brinker, T., & Gokaslan, Z. L. (2024). Clinical criteria for filum terminale resection in occult tethered cord syndrome. Journal of Neurosurgery: Spine, 40(6), 758-766. https://doi.org/10.3171/2024.1.SPINE231191
​
Klinge, P. M., Srivastava, V., McElroy, A., Leary, O. P., Ahmed, Z., Donahue, J. E., Brinker, T., De Vloo, P., & Gokaslan, Z. L. (2022). Diseased Filum Terminale as a Cause of Tethered Cord Syndrome in Ehlers-Danlos Syndrome: Histopathology, Biomechanics, Clinical Presentation, and Outcome of Filum Excision. World neurosurgery, 162, e492–e502. https://doi.org/10.1016/j.wneu.2022.03.038
​​
McGhee, K. (2025, December 29). Rethinking hEDS. Medical University of South Carolina. https://www.musc.edu/content-hub/News/2025/12/29/rethinking-heds
​
​