Subtle differences in autonomic symptoms in people diagnosed with hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders

Abstract

The hypermobile Ehlers–Danlos syndrome (hEDS) GENE study is a multicenter, cohort study with the goal to identify genes associated with hypermobile EDS. Of the 148 people enrolled in the hEDS GENE study, 98 meet the 2017 hEDS criteria, 27 have a hypermobility spectrum disorder (HSD) and 23 are asymptomatic family members. More than 80% of participants are female with an average age of 41 years. Each participant has completed seven questionnaires to quantify disease‐related symptomatology. People with hypermobility experience a variety of physical and somatic symptoms, especially in the areas of fatigue, kinesiophobia, gastrointestinal, and autonomic function. These cause a significant decrease in health‐related quality of life. The frequency and severity of most symptoms were indistinguishable between participants with hEDS and HSD; however, there were significant differences in autonomic symptoms. Less than 20% of participants had autoantibodies known to be associated with dysautonomia. Subtle symptomatic differences in people meeting the 2017 diagnostic criteria suggest focusing further etiologic studies on autonomic pathways.

RNA-Seq of Dermal Fibroblasts from Patients with Hypermobile Ehlers–Danlos Syndrome and Hypermobility Spectrum Disorders Supports Their Categorization as a Single Entity with Involvement of Extracellular Matrix Degrading and Proinflammatory Pathomechanisms

“…These JHM-associated comorbidities include chronic fatigue, pelvic floor problems, bladder dysfunction, increased susceptibility to osteoarthritis, various dysautonomic features (e.g., postural orthostatic tachycardia syndrome, gastrointestinal dysfunction), alterations of the immune system, headache/migraine, sleep disorders, behavioral disturbances, and psychological distress [ 1 , 2 , 3 , 4 , 5 , 6 ]. After the publication of the updated diagnostic criteria, several authors raised serious doubts about their limits, and it is still debated if hEDS and HSD are distinct clinical entities rather than part of a phenotypic spectrum that require a similar pattern of multidisciplinary intervention [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Considering the overlapping clinical presentation of hEDS and HSD patients and the absence of any objective and validated diagnostic biomarker, many researchers currently use the terms hEDS and HSD interchangeably and these two diagnostic labels are often grouped together as hEDS/HSD [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Recent advances in autonomic neurology: An overview

“…In particular, hypermobile EDS is known to present with an autonomic dysfunction, such as functional gastrointestinal disorders and orthostatic intolerance, including postural orthostatic tachycardia syndrome. [52][53][54][55][56][57] These autonomic symptoms are frequent extraarticular manifestations of hypermobile EDS and contribute to the disease burden. 58 Several previous studies confirmed the presence of cardiovascular and sudomotor dysfunction, and many upper and lower gastrointestinal symptoms increased along with worsened severity of joint hypermobility syndrome phenotype.…”

“…58 Several previous studies confirmed the presence of cardiovascular and sudomotor dysfunction, and many upper and lower gastrointestinal symptoms increased along with worsened severity of joint hypermobility syndrome phenotype. [52][53][54][55][56][57][58] However, it is still unclear how autonomic dysfunction occurs in EDS. Brooks et al 53 reported that patients hospitalized with EDS were 3.88 times more likely to have a food allergy and 6.16 times more likely to have cardiovascular complications such as mitral valve disorders, aortic aneurysm, and cardiac dysrhythmias than hospitalized patients without EDS.…”

“…In particular, hypermobile EDS is known to present with an autonomic dysfunction, such as functional gastrointestinal disorders and orthostatic intolerance, including postural orthostatic tachycardia syndrome 52–57 . These autonomic symptoms are frequent extra‐articular manifestations of hypermobile EDS and contribute to the disease burden 58 .…”

“…These autonomic symptoms are frequent extra‐articular manifestations of hypermobile EDS and contribute to the disease burden 58 . Several previous studies confirmed the presence of cardiovascular and sudomotor dysfunction, and many upper and lower gastrointestinal symptoms increased along with worsened severity of joint hypermobility syndrome phenotype 52–58 . However, it is still unclear how autonomic dysfunction occurs in EDS.…”