Ehlers–Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study

Published:March 31, 2014DOI:


      • We compare the prevalence of EDS within POTS patients.
      • The prevalence of EDS amongst patients with POTS is statistically significant.
      • We suspect that EDS may be a predictor of POTS.



      This study examines a possible relationship between Ehlers–Danlos Syndrome (EDS) and Postural Tachycardia Syndrome (POTS).


      We retrospectively reviewed 109 medical records of patients suffering from autonomic dysfunction exhibiting at least one POTS symptom from one urban clinic for EDS and POTS diagnoses between 2006 and 2013. The presence of EDS within the POTS and non-POTS populations was calculated and compared to that of the general population.


      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 statistically significant difference from the suggested prevalence of EDS in the general population of 0.02% (p < 0.0001). 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%), a statistically significant difference from the general population (p < 0.0001). The prevalence of EDS was significantly higher in the POTS group compared to the non-POTS group (p = 0.0329). The odds ratio comparing the odds of EDS for POTS versus non-POTS patients is 4.9 (95% CI: 1.2, 20.1).


      The presence of EDS may be significantly higher in patients with POTS than that of the general population and in autonomic patients without POTS. We suspect an additional underlying mechanism of POTS caused by EDS.


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        • Low P.A.
        • Opfer-Gehrking T.
        • Textor S.C.
        • Benarroch E.E.
        • Win-Kuang S.
        • Schondorf R.
        • et al.
        Postural tachycardia syndrome (POTS).
        Neurology [Internet]. Lippincott Williams & Wilkins, 1995 ([cited 2013 Jun 25];45(4):S19–S25. Available from:])
        • Jacob G.
        • Costa F.
        • Shannon J.
        • Roberston R.
        • Wathen M.
        • Stein M.
        • et al.
        The neuropathic postural tachycardia syndrome.
        N Engl J Med. 2000; 343: 1008-1014
        • Streeten P.
        • Health Y.
        Pathogenesis of hyperadrenergic orthostatic hypotension.
        J Clin Invest. 1990; 86 ([(November)]): 1582-1588
        • Masuki S.
        • Eisenach J.H.
        • Schrage W.G.
        • Johnson C.P.
        • Dietz N.M.
        • Wilkins B.W.
        • et al.
        Reduced stroke volume during exercise in postural tachycardia syndrome.
        J Appl Physiol [Internet]. 2007 Oct [cited 2013 Jun 25]; 103 (Available from: 1128-1135
        • Joyner M.J.
        • Masuki S.
        POTS versus deconditioning: the same or different?.
        Clin Auton Res [Internet]. 2008 Dec [cited 2013 Jun 25]; 18 (Available from: 300-307
        • Streeten D.
        • Thomas D.
        • Bell D.
        the roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome.
        Am J Med. 2000; 320: 1-8
        • Raj S.
        • Robertson D.
        Blood volume perturbations in the postural tachycardia syndrome.
        Am J Med. 2007; 334: 57-60
        • Medow M.S.
        Defects in cutaneous angiotensin converting enzyme 2 and angiotensin-(1–7) production in postural tachycardia syndrome.
        . 2010; 53: 767-774
        • Gazit Y.
        • Nahir A.M.
        • Grahame R.
        • Jacob G.
        Dysautonomia in the joint hypermobility syndrome.
        Am J Med [Internet]. 2003 Jul [cited 2013 Jun 25]; 115 (Available from: 33-40
        • Hakim A.
        • Grahame R.
        Joint hypermobility.
        Best Pract Res Clin Rheumatol. 2003; 17 ([[Internet] Available from:]): 989-1004
        • Benarroch E.
        Postural tachycardia syndrome: a heterogeneous and multifactorial disorder.
        Mayo Clin. Proc.87(12). Elsevier Inc., Dec 2012 ([[Internet]. Dec [cited 2013 Jun 25]. Available from:])
        • Thould A.K.
        • Beighton P.
        The Ehlers–Danlos syndrome.
        Ann Rheum Dis. 1970; 29: 332-333
        • Rowe P.C.
        • Barron D.F.
        • Calkins H.
        • Maumenee I.H.
        • Tong P.Y.
        • Geraghty M.T.
        Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers–Danlos syndrome.
        J Pediatr. 1999; 35 ([[Internet]. Available from:]): 494-499
        • Tucker D.H.
        • Miller E.
        • Jacoby W.J.
        Ehlers–Danlos syndrome with a sinus of valsalva aneurysm and aortic insufficiency simulating rheumatic heart disease.
        Am J Med. 1963; 35: 715-720
        • De Paepe a
        • Malfait F.
        The Ehlers–Danlos syndrome, a disorder with many faces.
        Clin Genet. [Internet]. 2012 Jul [cited 2013 Sep 16]; 82 (Available from: 1-11
        • Wenstrup R.
        • De Paepe A.
        Ehlers–Danlos syndrome , classic type.
        GeneReviews. 2007
        • Steinmann B.
        • Royce P.M.
        • Superti-Furga A.
        The Ehlers–Danlos syndrome.
        in: Royce P. Steinmann B. Connect. tissue its heritable Disord. Mol. Genet. Med. Asp. 2nd ed. Wiley-Liss, New York2002: 431-524
        • Kanjwal K.
        • Saeed B.
        • Karabin B.
        • Kanjwal Y.
        • Blair P.
        Comparative clinical profile of postural orthostatic tachycardia patients with and without joint hypermobility syndrome.
        Ind Pacing Electrophysiol J. 2010; 10: 173-178
        • Watanabe A.
        • Shimada T.
        The vascular type of Ehlers–Danlos syndrome.
        J Nippon Med Sch. 2008; 75: 254-261
        • Roach M.
        • Burton A.
        The reason for the shape of the distensibility curves of arteries.
        Can J Biochem. 1957; 35: 681-690
        • Samila Z.
        • Carter S.
        The effect of age on the unfolding of elastin lamellae and collagen fibers with stretch in human carotid arteries.
        Can J Physiol Pharmacol. 1981; 59: 1050-1057
        • De Paepe A.
        • Nuytinck L.
        • Hausser I.
        • Anton-Lamprecht I.
        • Naeraert J.-M.
        Mutations in the COL5A1 gene are causal in the Ehlers–Danlos syndromes I and II.
        Am J Hum Genet. 1997; 60: 547-554
        • Schalkwijk J.
        • Zweers M.
        • Steijlen P.
        • Dean W.
        • Taylor G.
        • Van Vlijmen I.
        • et al.
        A recessive form of Ehlers–Danlos syndrome caused by tenascin-X deficiency.
        N Engl J Med. 2001; 345: 547-554
        • Pepin M.
        • Schwarze U.
        • Superti-Furga A.
        • Byers P.H.
        Clinical and genetic features of Ehlers–Danlos syndrome type IV, the vascular type.
        . 2000; 342 ([Ne.]): 673-680
        • Tinkle B.T.
        • Ha Bird
        • Grahame R.
        • Lavallee M.
        • Levy H.P.
        • Sillence D.
        The lack of clinical distinction between the hypermobility type of Ehlers–Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome).
        Am J Med Genet A [Internet]. 2009 Nov [cited 2013 Sep 16]; 149A (Available from: 2368-2370