Dysautonomia in the Ehlers–Danlos syndromes and hypermobility spectrum disorders—With a focus on the postural tachycardia syndrome
Abstract
Dysautonomia (autonomic dysfunction) occurs in the Ehlers–Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Symptoms include palpitations, dizziness, presyncope, and syncope, especially when standing upright. Symptoms of orthostatic intolerance are usually relieved by sitting or lying and may be exacerbated by stimuli in daily life that cause vasodilatation, such as food ingestion, exertion, and heat. Neurocardiovascular dysautonomia may result in postural tachycardia syndrome (PoTS), a major cause of orthostatic intolerance. It is defined by a rise in heart rate of >30 beats per minute (bpm) in adults and >40 bpm in teenagers while upright, without a fall in blood pressure (BP; orthostatic hypotension). In some, it can be compounded by the presence of low BP. For many, there is delay in clinicians recognizing the nature of the symptoms, and recognizing EDS or HSD, leading to delays in treatment. The onset of PoTS may be linked to an event such as infection, trauma, surgery, or stress. Gastrointestinal and urinary bladder involvement may occur, along with thermoregulatory dysfunction. In some, the mast cell activation syndrome may be contributary, especially if it causes vasodilatation. This paper reviews neurocardiovascular dysautonomia with an emphasis on PoTS, its characteristics, associations, pathophysiology, investigation, and treatment.
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Dysautonomia occurs in up to 75% of patients with HSDs.
“Dysautonomia (up to 75%)”
From Hypermobility spectrum disorders: A review (2023) · cites this paper as [51]
Cites
The 2017 international classification of the Ehlers–Danlos syndromes
Malfait, F., Francomano, C., Byers, P., Belmont, J., Berglund, B., Black, J., Bloom, L., Bowen, J. M., Brady, A. F., Burrows, N. P., et al. (2017) · American Journal of Medical Genetics Part C: Seminars in Medical Genetics · doi:10.1002/ajmg.c.31552 · Cited by 1,936 · cited 1× · see citing works
“The relationship among joint hypermobility syndrome (JHS, i.e., pre-2017 changes in the criteria) (Castori et al., 2017; Malfait et al., 2017), hEDS, and cardiovascular autonomic dysfunction was extensively reviewed by A. Hakim, O'Callaghan, et al. (2017) and Roma, Marden, De Wandele, Francomano,…”
BackgroundSelf-citationA framework for the classification of joint hypermobility and related conditions
Castori, M., Tinkle, B., Levy, H., Grahame, R., Malfait, F., & Hakim, A. (2017) · American Journal of Medical Genetics Part C: Seminars in Medical Genetics · doi:10.1002/ajmg.c.31539 · Cited by 602 · cited 1× · see citing works
“The relationship among joint hypermobility syndrome (JHS, i.e., pre-2017 changes in the criteria) (Castori et al., 2017; Malfait et al., 2017), hEDS, and cardiovascular autonomic dysfunction was extensively reviewed by A. Hakim, O'Callaghan, et al. (2017) and Roma, Marden, De Wandele, Francomano,…”
BackgroundSelf-citationIdiopathic postural orthostatic tachycardia syndrome: An attenuated form of acute pandysautonomia?
Schondorf, R., & Low, P. A. (1993) · Neurology · doi:10.1212/wnl.43.1_part_1.132 · Cited by 548 · see citing works
Shaw, B. H., Stiles, L. E., Bourne, K., Green, E. A., Shibao, C. A., Okamoto, L. E., Garland, E. M., Gamboa, A., Diedrich, A., Raj, V., et al. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12895 · Cited by 326 · cited 1× · see citing works
“In a recent large survey, 3,276 individuals (83% of the study participants) reported being diagnosed by a physician with another medical condition in addition to PoTS (Shaw et al., 2019).”
BackgroundEndocrinology: Adult and Pediatric
(2016) · Elsevier eBooks · doi:10.1016/c2012-1-03052-4 · Cited by 305 · see citing works
Baur, V., Hänggi, J., Langer, N., & Jäncke, L. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.06.003 · Cited by 258 · see citing works
Postural tachycardia syndrome—current experience and concepts
Mathias, C. J., Low, D. A., Iodice, V., Owens, A. P., Kirbis, M., & Grahame, R. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.187 · Cited by 251 · cited 5× · see citing works
“Within the dysautonomia population, and often applicable to hypermobile EDS (hEDS) and HSD, a large group consist of those with intermittent autonomic malfunction, where between episodes there appear to be no obvious autonomic abnormalities, unlike in patients with autonomic failure (Mathias et al., 2011).”
BackgroundInfluentialSelf-citationInvestigation of autonomic disorders
Mathias, C. J., Low, D. A., Iodice, V., & Bannister, R. (2013) · Oxford University Press eBooks · doi:10.1093/med/9780198566342.003.0024 · Cited by 208 · see citing works
Self-citationExercise and non-pharmacological treatment of POTS
Fu, Q., & Levine, B. D. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.07.001 · Cited by 174 · see citing works
Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome
Raj, S. R., Black, B. K., Biaggioni, I., Harris, P. A., & Robertson, D. (2005) · Circulation · doi:10.1161/circulationaha.104.497594 · Cited by 171 · see citing works
Cardiovascular autonomic dysfunction in Ehlers–Danlos syndrome—Hypermobile type
Hakim, A., O'Callaghan, C., De Wandele, I., Stiles, L., Pocinki, A., & Rowe, P. (2017) · American Journal of Medical Genetics Part C: Seminars in Medical Genetics · doi:10.1002/ajmg.c.31543 · Cited by 163 · see citing works
Self-citationCaught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome
Ocon, A. J. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00063 · Cited by 162 · see citing works
Smit, A. J., Wieling, W., Fujimura, J., Denq, J., Opfer-Gehrking, T., Akarriou, M., Karemaker, J., & Low, P. (2004) · Clinical Autonomic Research · doi:10.1007/s10286-004-0187-x · Cited by 153 · see citing works
Physical manoeuvres for combating orthostatic dizziness in autonomic failure
LIESHOUT, J. J. V., ten Harkel, A. D. J., & Wieling, W. (1992) · The Lancet · doi:10.1016/0140-6736(92)90932-s · Cited by 152 · see citing works
Hakim, A. J. (2004) · Rheumatology · doi:10.1093/rheumatology/keh279 · Cited by 147 · see citing works
Self-citationChronic fatigue in Ehlers–Danlos syndrome—Hypermobile type
Hakim, A. J., Wandele, I. D., O'Callaghan, C., Pocinki, A. G., & Rowe, P. C. (2017) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31542 · Cited by 146 · see citing works
Self-citationWhat is brain fog? An evaluation of the symptom in postural tachycardia syndrome
Ross, A. J., Medow, M. S., Rowe, P. C., & Stewart, J. M. (2013) · Clinical Autonomic Research · doi:10.1007/s10286-013-0212-z · Cited by 141 · see citing works
Orthostatic intolerance in the chronic fatigue syndrome
Schondorf, R., Benoit, J., Wein, T., & Phaneuf, D. (1999) · Journal of the Autonomic Nervous System · doi:10.1016/s0165-1838(98)00177-5 · Cited by 141 · see citing works
Sleep Disturbances and Diminished Quality of Life in Postural Tachycardia Syndrome
Bagai, K., Song, Y., Ling, J. F., Malow, B., Black, B. K., Biaggioni, I., Robertson, D., & Raj, S. R. (2011) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.28110 · Cited by 134 · see citing works
Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome
Roma, M., Marden, C. L., De Wandele, I., Francomano, C. A., & Rowe, P. C. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.02.006 · Cited by 133 · see citing works
Psychiatric profile and attention deficits in postural tachycardia syndrome
Raj, V, Haman, K. L., Raj, S. R., Byrne, D., Blakely, R. D., Biaggioni, I., Robertson, D., & Shelton, R. C. (2009) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2008.144360 · Cited by 131 · see citing works
Cognitive and psychological issues in postural tachycardia syndrome
Raj, V., Opie, M., & Arnold, A. C. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.03.004 · Cited by 125 · see citing works
Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes
Cazzato, D., Castori, M., Lombardi, R., Caravello, F., Bella, E. D., Petrucci, A., Grammatico, P., Dordoni, C., Colombi, M., & Lauria, G. (2016) · Neurology · doi:10.1212/wnl.0000000000002847 · Cited by 122 · see citing works
Kucharik, A. H., & Chang, C. (2020) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-019-08755-8 · Cited by 122 · see citing works
Gunning, W. T., Kvale, H. M., Kramer, P. M., Karabin, B. L., & Grubb, B. P. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.119.013602 · Cited by 118 · see citing works
Mast cell disorders in Ehlers-Danlos syndrome
Seneviratne, S. L., Maitland, A., & Afrin, L. (2017) · American Journal of Medical Genetics Part C: Seminars in Medical Genetics · doi:10.1002/ajmg.c.31555 · Cited by 107 · see citing works
Autoimmunity in postural orthostatic tachycardia syndrome: Current understanding
Vernino, S., & Stiles, L. E. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.04.005 · Cited by 107 · cited 1× · see citing works
“There is recent and increasing evidence both on measurement of antibody levels and in response to immunotherapy that autoimmune mechanisms may be causative or contributory (Al-Ansari & Robertson, 2021; Gunning et al., 2019; Vernino & Stiles, 2018; Watari et al., 2018).”
BackgroundSingle centre experience of ivabradine in postural orthostatic tachycardia syndrome
McDonald, C., Frith, J., & Newton, J. L. (2011) · Europace · doi:10.1093/europace/euq390 · Cited by 105 · see citing works
Rosen, S. G., & Cryer, P. E. (1982) · The American Journal of Medicine · doi:10.1016/0002-9343(82)90559-9 · Cited by 104 · see citing works
Anderson, J. W., Lambert, E. A., Sari, C. I., Dawood, T., Esler, M. D., Vaddadi, G., & Lambert, G. W. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00230 · Cited by 96 · see citing works
Autoimmune postural orthostatic tachycardia syndrome
Watari, M., Nakane, S., Mukaino, A., Nakajima, M., Mori, Y., Maeda, Y., Masuda, T., Takamatsu, K., Kouzaki, Y., Higuchi, O., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.524 · Cited by 94 · cited 1× · see citing works
“There is recent and increasing evidence both on measurement of antibody levels and in response to immunotherapy that autoimmune mechanisms may be causative or contributory (Al-Ansari & Robertson, 2021; Gunning et al., 2019; Vernino & Stiles, 2018; Watari et al., 2018).”
BackgroundCoffin, S. T., Black, B. K., Biaggioni, I., Paranjape, S. Y., Orozco, C., Black, P. W., Dupont, W. D., Robertson, D., & Raj, S. R. (2012) · Heart Rhythm · doi:10.1016/j.hrthm.2012.05.002 · Cited by 88 · see citing works
(2013) · Oxford University Press eBooks · doi:10.1093/med/9780198566342.001.0001 · Cited by 75 · see citing works
Sleep-Disordered Breathing in Ehlers-Danlos Syndrome
Guilleminault, C., Primeau, M., Chiu, H.-Y., Yuen, K. M., Leger, D., & Metlaine, A. (2013) · Chest · doi:10.1378/chest.13-0174 · Cited by 68 · see citing works
Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome
Garland, E. M., Gamboa, A., Nwazue, V. C., Celedonio, J. E., Paranjape, S. Y., Black, B. K., Okamoto, L. E., Shibao, C. A., Biaggioni, I., Robertson, D., et al. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.03.005 · Cited by 65 · see citing works
Treatment of postural tachycardia syndrome: a comparison of octreotide and midodrine
Hoeldtke, R. D., Bryner, K. D., Hoeldtke, M. E., & Hobbs, G. (2006) · Clinical Autonomic Research · doi:10.1007/s10286-006-0373-0 · Cited by 57 · see citing works
Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review
Mehr, S. E., Barbul, A., & Shibao, C. A. (2018) · Clinical Autonomic Research · doi:10.1007/s10286-018-0519-x · Cited by 55 · see citing works
Schofield, J. R., & Chemali, K. R. (2019) · American Journal of Therapeutics · doi:10.1097/mjt.0000000000000778 · Cited by 55 · see citing works
Copetti, M., Morlino, S., Colombi, M., Grammatico, P., Fontana, A., & Castori, M. (2019) · Rheumatology · doi:10.1093/rheumatology/kez029 · Cited by 55 · see citing works
Risk Factors for Postural Tachycardia Syndrome in Children and Adolescents
Lin, J., Han, Z., Li, X., Ochs, T., Zhao, J., Zhang, X., Yang, J., Liu, P., Xiong, Z., Gai, Y., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113625 · Cited by 54 · see citing works
Alomari, M., Hitawala, A., Chadalavada, P., Covut, F., Al Momani, L., Khazaaleh, S., Gosai, F., Al Ashi, S., Abushahin, A., & Schneider, A. (2020) · Cureus · doi:10.7759/cureus.7881 · Cited by 53 · cited 1× · see citing works
“In addition, PoTS is increasingly recognized as being associated with gastroparesis and functional gastrointestinal disorders (FGID) (Alomari et al., 2020; Mehr, Barbul, & Shibao, 2018; Tu, Abell, Raj, & Mar, 2020).”
BackgroundMallien, J., Isenmann, S., Mrazek, A., & Haensch, C. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00118 · Cited by 52 · see citing works
Weinstock, L. B., Brook, J. B., Myers, T. L., & Goodman, B. P. (2018) · BMJ Case Reports · doi:10.1136/bcr-2017-221405 · Cited by 51 · see citing works
Kovacic, K., Kolacz, J., Lewis, G. F., & Porges, S. W. (2020) · American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000753 · Cited by 51 · see citing works
The management of adult patients with severe chronic small intestinal dysmotility
Nightingale, J. M. D., Paine, P., McLaughlin, J. T., Emmanuel, A. V., Martin, J. E., & Lal, S. (2020) · Gut · doi:10.1136/gutjnl-2020-321631 · Cited by 50 · see citing works
Ruzieh, M., Baugh, A., Dasa, O., Parker, R. L., Perrault, J. T., Renno, A., Karabin, B. L., & Grubb, B. (2017) · Journal of Interventional Cardiac Electrophysiology · doi:10.1007/s10840-017-0225-y · Cited by 48 · see citing works
Obstructive sleep apnoea and quality of life in Ehlers-Danlos syndrome: a parallel cohort study
Gaisl, T., Giunta, C., Bratton, D. J., Sutherland, K., Schlatzer, C., Sievi, N., Franzen, D., Cistulli, P. A., Rohrbach, M., & Kohler, M. (2017) · Thorax · doi:10.1136/thoraxjnl-2016-209560 · Cited by 47 · see citing works
Tai, F. W. D., Palsson, O. S., Lam, C. Y., Whitehead, W. E., Sperber, A. D., Tornblom, H., Simren, M., & Aziz, I. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.13975 · Cited by 44 · see citing works
The genesis and presentation of anxiety in disorders of autonomic overexcitation
Owens, A. P., Low, D. A., Iodice, V., Critchley, H. D., & Mathias, C. J. (2017) · Autonomic Neuroscience · doi:10.1016/j.autneu.2016.10.004 · Cited by 41 · see citing works
Self-citationHakim, A. J., Tinkle, B. T., & Francomano, C. A. (2021) · American Journal of Medical Genetics Part C: Seminars in Medical Genetics · doi:10.1002/ajmg.c.31954 · Cited by 37 · see citing works
Self-citationNeurovisceral phenotypes in the expression of psychiatric symptoms
Eccles, J., Owens, A. P., Mathias, C. J., Umeda, S., & Critchley, H. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00004 · Cited by 36 · see citing works
Self-citationIvabradine for the Treatment of Postural Orthostatic Tachycardia Syndrome: A Systematic Review
Gee, M. E., Watkins, A. K., Brown, J. N., & Young, E. (2018) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-017-0252-1 · Cited by 35 · see citing works
Multimodal Biomarkers Quantify Recovery in Autoimmune Autonomic Ganglionopathy
Koay, S., Vichayanrat, E., Bremner, F., Panicker, J. N., Lang, B., Lunn, M. P., Watson, L. P. E., Ingle, G. T., Hagen, E. M., McNamara, P., et al. (2021) · Annals of Neurology · doi:10.1002/ana.26018 · Cited by 34 · see citing works
Self-citationImmunomodulatory treatment in postural tachycardia syndrome: A case series
Rodriguez, B., Hoepner, R., Salmen, A., Kamber, N., & Z'Graggen, W. J. (2020) · European Journal of Neurology · doi:10.1111/ene.14711 · Cited by 29 · see citing works
Mechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome
Tu, Y., Abell, T. L., Raj, S. R., & Mar, P. L. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.14031 · Cited by 26 · see citing works
Sleep disorders in patients with postural tachycardia syndrome
Miglis, M. G., Muppidi, S., Feakins, C., Fong, L., Prieto, T., & Jaradeh, S. (2016) · Clinical Autonomic Research · doi:10.1007/s10286-015-0331-9 · Cited by 25 · see citing works
Owens, A. P., Low, D. A., Critchley, H., & Mathias, C. J. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.01.004 · Cited by 25 · see citing works
Self-citationBourne, K. M., Hall, J., Stiles, L. E., Sheldon, R. S., Shibao, C. A., Okamoto, L. E., Garland, E. M., Gamboa, A. C., Peltier, A., Diedrich, A., et al. (2021) · CJC Open · doi:10.1016/j.cjco.2021.08.014 · Cited by 24 · see citing works
Pengo, M. F., Higgins, S., Drakatos, P., Martin, K., Gall, N., Rossi, G. P., & Leschziner, G. (2015) · Sleep Medicine · doi:10.1016/j.sleep.2015.08.003 · Cited by 21 · see citing works
Postural tachycardia syndrome with asystole on head-up tilt
Alshekhlee, A., Guerch, M., Ridha, F., McNeeley, K., & Chelimsky, T. C. (2007) · Clinical Autonomic Research · doi:10.1007/s10286-007-0445-9 · Cited by 18 · see citing works
Bagai, K., Peltier, A. C., Malow, B. A., Diedrich, A., Shibao, C. A., Black, B. K., Paranjape, S. Y., Orozco, C., Biaggioni, I., Robertson, D., et al. (2016) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.5806 · Cited by 17 · see citing works
Joint hypermobility and autonomic hyperactivity: an autonomic and functional neuroimaging study
Eccles, J., Owens, A. P., Harrison, N. A., Grahame, R., & Critchley, H. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00427-x · Cited by 13 · see citing works
Self-citationMathias, C. J., & Young, T. (2003) · Clinical Autonomic Research · doi:10.1007/s10286-003-0092-8 · Cited by 12 · see citing works
Self-citationDecreased orthostatic adrenergic reactivity in non-dipping postural tachycardia syndrome
Figueroa, J. J., Bott-Kitslaar, D. M., Mercado, J. A., Basford, J. R., Sandroni, P., Shen, W.-K., Sletten, D. M., Gehrking, T. L., Gehrking, J. A., Low, P. A., et al. (2014) · Autonomic Neuroscience · doi:10.1016/j.autneu.2014.06.003 · Cited by 12 · see citing works
Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder
Hakim, A. J. (2019) · Lara D. Veeken · doi:10.1093/rheumatology/kez134 · Cited by 7 · see citing works
Self-citationAutonomic Aspects of Neurology
Mathias, C. J., Ingle, G. T., & Iodice, V. (2016) · doi:10.1002/9781118486160.ch24 · Cited by 5 · see citing works
Self-citationOrthostatic Hypotension and Orthostatic Intolerance
Mathias, C. J., Iodice, V., Low, D. A., & Galizia, G. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00113-x · Cited by 4 · see citing works
Self-citationThe Autonomic Laboratory for Evaluating Syncope/Collapse: Investigations and Their Implications
Mathias, C. J., Owens, A. P., & Iodice, V. (2020) · Springer eBooks · doi:10.1007/978-3-030-44507-2_19 · Cited by 2 · see citing works
Self-citationPostural orthostatic tachycardia syndrome: insights into pathogenesis and treatment
Al-Ansari, A., & Robertson, N. P. (2021) · Journal of Neurology · doi:10.1007/s00415-021-10649-9 · Cited by 2 · see citing works
Plugging the leak - Benefits of the vasopressin-2 agonist, desmopressin in autonomic failure
Mathias, C., & Young, T. (2003) · UCL Discovery (University College London) · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
1 of the 71 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Hypermobility spectrum disorders: A review
Carroll, M. B. (2023) · Rheumatology and Immunology Research · doi:10.2478/rir-2023-0010 · Cited by 45 · see citing works
Aziz, Q., Harris, L. A., Goodman, B. P., Simrén, M., & Shin, A. (2025) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2025.02.015 · Cited by 27 · see citing works
Conway, A. E., Verdi, M., Shaker, M. S., Bernstein, J. A., Beamish, C., Morse, R., Madan, J. C., Lee, M. W., Sussman, G., Al-Nimr, A., et al. (2024) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2024.03.019 · Cited by 24 · see citing works
Arnaert, S., Arts, J., Raymenants, K., Baert, F., & Delsupehe, K. (2024) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm23099 · Cited by 23 · see citing works
Ritelli, M., Chiarelli, N., Cinquina, V., Vezzoli, M., Venturini, M., & Colombi, M. (2023) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.63426 · Cited by 22 · see citing works
Hypermobile Ehlers-Danlos Syndrome: Cerebrovascular, Autonomic and Neuropathic Features
Novák, P., Systrom, D. M., Marciano, S. P., Witte, A. V., Warren, A., Felsenstein, D., Giannetti, M. P., Hamilton, M. J., Nicoloro‐SantaBarbara, J. M., Castells, M., et al. (2025) · American Journal of Medicine Open · doi:10.1016/j.ajmo.2025.100111 · Cited by 18 · see citing works
Mast Cell Involvement in the Pathogenesis of Selected Musculoskeletal Diseases
Gutowski, Ł., Kanikowski, S., & Formanowicz, D. (2023) · Life · doi:10.3390/life13081690 · Cited by 14 · see citing works
Sivan, M., Corrado, J., Leeds, U., & Mathias, C. J. (2022) · Advances in Clinical Neuroscience & Rehabilitation · doi:10.47795/qkbu6715 · Cited by 14 · see citing works
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Lindberg, G., & Mohammadian, G. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1141035 · Cited by 8 · see citing works
Genetic and functional analysis of Raynaud’s syndrome implicates loci in vasculature and immunity
Tervi, A. M., Ramste, M. O., Abner, E., Cheng, P. P., Lane, J. M., Maher, M., Valliere, J. T., Lammi, V., Strausz, S. J., Riikonen, J., et al. (2024) · Cell Genomics · doi:10.1016/j.xgen.2024.100630 · Cited by 7 · see citing works
Navigating Complexity in Postural Orthostatic Tachycardia Syndrome
Qu, H., & Hakonarson, H. H. (2024) · Biomedicines · doi:10.3390/biomedicines12081911 · Cited by 7 · see citing works
Ryu, T., Adler, B. L., Jeong, S. J., Lee, D. C., Höke, A., Na, C. H., & Chung, T. (2025) · Autonomic Neuroscience · doi:10.1016/j.autneu.2025.103247 · Cited by 6 · see citing works
Long COVID and hypermobility spectrum disorders have shared pathophysiology
Ganesh, R., & Munipalli, B. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1455498 · Cited by 7 · see citing works
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Grach, S. L., Dudenkov, D. V., Pollack, B., Fairweather, D., Aakre, C. A., Munipalli, B., Croghan, I. T., Mueller, M. R., Overgaard, J. D., Bruno, K. A., et al. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1482917 · Cited by 7 · see citing works
Ziaks, L., Johnson, K., Schiltz, K., Pelo, R. M., Lamotte, G. J., Molin, C. D., Chung, T., & Cortez, M. M. (2024) · Archives of Rehabilitation Research and Clinical Translation · doi:10.1016/j.arrct.2024.100366 · Cited by 6 · see citing works
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Chambers, P. W. (2024) · Qeios · doi:10.32388/je31eo.5 · Cited by 5 · see citing works
Torres, R., Cash, E. D., & Levinson, C. A. (2025) · International Journal of Eating Disorders · doi:10.1002/eat.24462 · Cited by 4 · see citing works
Валентинович, П. К., Volkov, D. A., & Кirov, М. Y. (2023) · General Reanimatology · doi:10.15360/1813-9779-2023-5-2352 · Cited by 4 · see citing works
Logarbo, B. P., Yang, M., Longo, M. T., Kingry, C., & Courseault, J. (2023) · PM&R · doi:10.1002/pmrj.13120 · Cited by 5 · see citing works
Complex breathlessness in postural tachycardia syndrome and autonomic dysfunction
Gall, N. P., & Reilly, C. C. (2022) · European Respiratory Society eBooks · doi:10.1183/2312508x.10013621 · Cited by 2 · see citing works
Managing hypermobility spectrum disorder in a psychiatric setting
Stevenson, H., & Khairova, R. A. (2025) · BMJ Case Reports · doi:10.1136/bcr-2024-264159 · Cited by 1 · see citing works
Kaabi, N. A., Camacho, E., Orchanian‐Cheff, A., Silano, V., McGillis, L., Truong, W. T., Reid, W. D., Chow, C., Ryan, C. M., Slepian, P. M., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14124126 · Cited by 2 · see citing works
Voice Disorders in Ehlers–Danlos Syndrome
Venkatraman, A., Schenck, A., & Thibeault, S. L. (2025) · American Journal of Speech-Language Pathology · doi:10.1044/2025_ajslp-25-00069 · Cited by 1 · see citing works
Orabi, Z. A., Thompson, S., van Vliet, J., Gee, K., Roy, A., & Townend, J. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14207373 · Cited by 1 · see citing works
Cuenca-Gómez, J. A., Dawid-Milner, M. S., & Sánchez‐Martínez, R. (2026) · Revista Clínica Española (English Edition) · doi:10.1016/j.rceng.2026.502457 · Cited by 1 · see citing works
Effect of Comorbid Dysautonomia on Postoperative Complications in Sinonasal Surgery
Dawood, E., Saeedi, A., & Schuman, T. A. (2026) · American Journal of Rhinology and Allergy · doi:10.1177/19458924251413870 · Cited by 1 · see citing works
Almutairi, N. A., Greenwood, D., & Sivan, M. (2026) · Rheumatology Advances in Practice · doi:10.1093/rap/rkag034 · Cited by 1 · see citing works
Dhaybi, O. A., & Bhatt, D. L. (2026) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000001295 · Cited by 1 · see citing works
Comorbid Conditions of Ehlers–Danlos Syndromes and Vulvodynia: A Latent Class Analysis
Glayzer, J. E., Bray, B. C., Kobak, W. H., Trujillo, C., Patil, C. L., Li, H., Francomano, C. A., & Schlaeger, J. M. (2026) · Pain Management Nursing · doi:10.1016/j.pmn.2026.03.005 · Cited by 1 · see citing works
Britton, D., Stonick, K., Lopez, D., & Graville, D. J. (2026) · Dysphagia · doi:10.1007/s00455-026-10952-5 · Cited by 1 · see citing works
Introduction: An overview of the Ehlers-Danlos syndromes and hypermobility spectrum disorders
Francomano, C. A., Hakim, A. J., Henderson, L. G. S., & Henderson, F. C. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95082-4.00061-x · Cited by 1 · see citing works
Self-citationThe α 2A -adrenergic receptor ( ADRA2A ) modulates susceptibility to Raynaud’s syndromePreprint
Tervi, A. M., Ramste, M. O., Abner, E., Cheng, P. P., Lane, J. M., Maher, M., Lammi, V., Strausz, S. J., Nguyen, T., Lago‐Docampo, M., et al. (2023) · medRxiv · doi:10.1101/2023.10.04.23296526 · Cited by 1 · see citing works
Pearson, M. L., Laraway, B. J., Elias, E. R., Bilousova, G., & Haendel, M. A. (2025) · medRxiv · doi:10.1101/2025.10.22.25338573 · Cited by 1 · see citing works
Clarke, J. E., Santana, J., & Manjarrez, E. C. (2022) · Annals of Internal Medicine Clinical Cases · doi:10.7326/aimcc.2022.0154
The α 2A-Adrenergic Receptor ( ADRA2A) Modulates Susceptibility to Raynaud's SyndromePreprint
Tervi, A. M., Ramste, M. O., Abner, E., Cheng, P. P., Lane, J. M., Maher, M., Lammi, V., Strausz, S. J., Nguyen, T., Lago‐Docampo, M., et al. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4653172
Musculoskeletal Cases: Chronic Musculoskeletal Pain and Fatigue
Francomano, C. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-816478-5.00071-6
Karrento, K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95082-4.00048-7
Chiron, A., Fernandez, A., Schmidt, L., Wüthrich, S. P., Suter, M. R., Leknes, S., & Berna, C. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.03.601919
Cesarean Delivery in a Patient With Hypermobile Ehlers-Danlos Syndrome: A Case Report
Antunes, B., Araújo, M., Noversa, C., Pedreira, J., & Marques, M. (2024) · Cureus · doi:10.7759/cureus.70667
Novák, P., Marciano, S. P., & Knief, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-12642-0.00022-0
Flegge, L. G., Estrella, E., Harris, E. K., Hirsh, A. T., & Bushey, M. A. (2025) · Frontiers in Pain Research · doi:10.3389/fpain.2025.1472160
Sweerts, K. W. E., Mujagic, Z., Keszthelyi, D., & Conchillo, J. M. (2025) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.70157
Parasympathetic and Sympathetic Nervous System Dysfunction and Monitoring
DePace, N. L., Soloway, S., Yayac, M. F., & Colombo, J. (2025) · Springer eBooks · doi:10.1007/978-3-031-88769-7_13
DePace, N. L., Soloway, S., Yayac, M. F., & Colombo, J. (2025) · Springer eBooks · doi:10.1007/978-3-031-88769-7_7
Cherchi, M. (2025) · Springer eBooks · doi:10.1007/978-3-031-94841-1_176
Cuenca-Gómez, J. A., Dawid-Milner, M. S., & Sánchez-Martín, R. (2026) · Revista Clínica Española · doi:10.1016/j.rce.2025.502457
Assessing the Risk of Gynecologic and Obstetric Diagnoses in Patients with Ehlers–Danlos Syndromes
Imbroane, M. R., Kim, H., Akesson, C., & Richards, E. G. (2026) · Journal of Women s Health · doi:10.1177/15409996261418483
Müller, K., Thiel, J. C., Schopen, L., Fimm, B., Schulz, J. B., & Maier, A. (2026) · Clinical Autonomic Research · doi:10.1007/s10286-026-01191-7
Chronic Dislocations and Pain in a College Athlete
Walker, T. K., Letocha, A. D., Kronk, R. A., Whitt, K. J., Himes, D. O., & Joseph, R. A. (2026) · The Journal for Nurse Practitioners · doi:10.1016/j.nurpra.2026.105737
Kim, S., Zhou, M., Kaelber, D. C., Talcott, K. E., & Singh, R. P. (2026) · Eye · doi:10.1038/s41433-026-04496-z
Too high and too loose: dysautonomia and the hypertensive paradox in hypermobility disorders
Johnson, J. W., Mirro, I., & Kontorovich, A. (2026) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000001310
Tudini, F. T., Crews-Stowe, C., & Levine, D. F. (2026) · Healthcare · doi:10.3390/healthcare14111573
Ingram, L. A., Tomkinson, G. R., Gower, B., d’Unienville, N. M. A., Boyle, T., Lang, J. J., & Bennett, H. (2026) · Research Square · doi:10.21203/rs.3.rs-9636462/v1
Ingram, L. A., Tomkinson, G. R., Gower, B., d’Unienville, N. M. A., Boyle, T., Lang, J. J., & Bennett, H. (2026) · Research Square · doi:10.21203/rs.3.rs-9636710/v1
The hypermobility crisis: A review and call to action
Motlak, M., Lee, E., Guilarte, G., Surapaneni, A., Dreikorn, E., Massart, M., & Choudhary, S. (2026) · Developmental Dynamics · doi:10.1002/dvdy.70169
Audio-vestibular manifestations of Ehlers-Danlos syndrome
Cherchi, M. (2026) · Future Rare Diseases · doi:10.1080/23995270.2026.2701706
Tamilson, B., Fenske, O., Morrin, H., Coebergh, J., Agrawal, N., Owens, A., Lim, P., & Poole, N. (2026) · Swiss Archives of Neurology, Psychiatry and Psychotherapy · doi:10.3390/sanpp176020010
Self-citationChiron, A., Fernandez, A., Schmidt, L., Wüthrich, S. P., Suter, M. R., Leknes, S., & Berna, C. (2026) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2026.100378
Ay, B. K., Seyithanoğlu, M., Kuzu, A. R., & Gülkesen, A. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15187332
Azabou, É., Bao, G., Pillot, A., Mehlal, S., Valdenaire, E., Jarnet, C., Gillas, F., Zagdoun, M., Vierne, B., Rangon, C.-M., et al. (2026) · Neurological Sciences · doi:10.1007/s10072-026-09420-7
Boris, J. R., & Bernadzikowski, T. (2026) · Clinical Autonomic Research · doi:10.1007/s10286-026-01242-z
Aphantasia beyond imagery: Interoception, neurodevelopment, and early experience
Nagai, Y., Gao, W., & Silvanto, J. (2026) · Personality and Individual Differences · doi:10.1016/j.paid.2026.114123
- Authors
- Mathias, C. J., Owens, A., Iodice, V., & Hakim, A.
- Affiliations
- University College London Hospitals NHS Foundation Trust (GB)
- King's College London (GB)
- The Wellington Hospital (GB)
- Corresponding author
- Hakim, Alan
- Venue
- American Journal of Medical Genetics Part C: Seminars in Medical Genetics
- Publisher
- Wiley
- Published
- 2021-11-12
- Volume
- 187
- Issue
- 4
- Pages
- 510-519
- ISSN
- 1552-4868 (ISSN-L)
- 1552-4876
- OpenAlex
- W3211807389
- Cited by
- 65
- References
- 71
- Citations by year
- 2026: 23 · 2025: 14 · 2024: 16 · 2023: 9 · 2022: 3
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part C Seminars in Medical Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- autonomic dysfunction, Ehlers-Danlos syndrome, hypermobility spectrum disorders, postural orthostatic tachycardia syndrome, orthostatic intolerance, syncope, mast cell activation syndrome, vasodilation, thermoregulatory dysfunction, gastrointestinal involvement, urinary bladder involvement, pathophysiology, diagnosis, treatment
- MeSH terms
- Mast Cell Activation Syndrome, Adolescent, Ehlers-Danlos Syndrome, Humans, Primary Dysautonomias, Postural Orthostatic Tachycardia Syndrome
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