Ehlers–Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study
Introduction
Postural Tachycardia Syndrome (POTS) is a common form of orthostatic intolerance with an unknown incidence across various ages. Patients suffering from POTS experience an increase in heart rate of greater than 30 beats per minute when moving from a supine to upright position. Adolescents, however, are held to a slightly more strict threshold of an increase in heart rate greater than 40 beats per minute. Patients generally experience lightheadedness, dimming of vision, confusion, anxiety and other symptoms that occur upon standing, suffering substantial disability and may be relieved upon sitting or lying down [1], [2].
The etiology of POTS is presently unknown. Studies, however, do present mechanisms and subtypes of POTS, including the neuropathic subtype [1], [2], the hyperadrenergic subtype [1], [3] the physical deconditioning mechanism [4], [5] and the volume dysregulation mechanism [6], [7], [8]. Additionally, studies have linked joint hypermobility syndrome with POTS [9], [10], [11], providing a potential link between Ehlers–Danlos Syndrome (EDS) and POTS.
EDS is a heterogeneous group of inherited abnormalities of connective tissue characterized by skin hyper-extensibility, joint hypermobility, and connective tissue fragility [12], [13]. The mechanistic relationship between EDS and POTS has been considered and suggested; vascular insufficiencies have been witnessed in patients with EDS [13], [14]. In this retrospective study, medical records of 109 individuals were reviewed for POTS and EDS in order to determine if EDS is a predictor of POTS by analyzing the presence of EDS amongst patients with POTS than amongst the general population. Furthermore, concurrent genetic testing of our patients was employed to ensure definitive EDS diagnosis. De Paepe et al. have performed extensive work in this area and have updated the Villefranche classification scheme with a more granular classification scheme, consisting of twelve subtypes, which we follow in this study [15].
Section snippets
Material and methods
We retrospectively reviewed 109 medical records of patients suffering from autonomic dysfunction exhibiting at least one POTS symptom from a single, subspecialty neurological urban clinic for EDS and POTS diagnoses between 2006 and 2013. The clinic predominantly treats patients with movement disorders and autonomic dysfunction referred from primary care physicians, cardiologists and general neurologists. The cohort was established by screening the medical records in the neurology department for
Results
The review revealed 39 (36F:3M) patients with POTS (mean ± SD age, 32.5 ± 11.8 years) with 7 cases of EDS yielding a prevalence of 18% (95% exact CI: 8%, 34%), a highly statistically significant difference to the suggested prevalence of EDS in the general population at 1 in 5000, or 0.02% (p < 0.0001) [17]. 70 patients (53F:17M) without POTS (mean ± SD age, 51.1 ± 14.7 years) contained 3 cases of EDS, yielding a prevalence of 4% (95% exact CI: 1%, 12%), also a statistically significant difference to the
Discussion
Researchers have discovered and created different classifications and mechanisms to describe POTS, yet the etiology of most POTS cases is unknown. One potential mechanism that has not been exhaustively researched is the relationship between joint hypermobility syndrome (JHS) and autonomic dysfunction, such as in POTS. Gazit et al. have studied the effects of JHS on the peripheral nervous system and demonstrated a relationship between the autonomic nervous system-related symptoms and JHS,
Study limitations
This study is the largest analysis of POTS patients and genetically confirmed EDS patients; obtaining a large data set is difficult in this patient population because of the low prevalence of POTS. The current scope of this study focused the EDS genetic analysis on the POTS patients; further expansion of this analysis to all autonomic dysfunction patients may provide us with higher rates in those patients. A definitive diagnosis of POTS requires tilt-table testing which all of our POTS patients
Conclusion
The presence of EDS may be higher in patients with POTS than that of the general population or in non-POTS autonomic dysfunction patients. With this new data, we suspect that EDS may be a predictor of POTS and that there may be an additional underlying mechanism of POTS caused by the change in connective tissue from EDS. Future studies on the genetics of EDS are currently ongoing; detail from those studies may help in revising the proposed mechanisms.
Conflict of interest and IRB approval
On behalf of all authors, the corresponding author states that there is no conflict of interest. Furthermore, this study was IRB approved. All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Acknowledgments
The authors thank the Boston University School of Medicine and the Medical Student Summer Research Program for providing guidance for this project.
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