recently published evidence supporting the involvement of FKBP14, alias FKBP22, in the molecular ensemble for type III, type VI, and type X collagen maturation, showing that the protein interacts with these types of collagens. Remarkably, mutations in type III and type VI collagens are the genetic hallmark of the vascular type of EDS (vEDS) and of COL6-related dystrophies, respectively.
Very few studies have assessed treatment options in patients with functional heartburn rigorously. In NERD patients, the symptoms response rate after four weeks of standard dose PPI therapy ranges between 46% and 57%.15,64 This surprisingly low response rate is almost 10-30% less than what has been observed in patients with erosive oesophagitis receiving a similar dose.65 The functional heartburn group is likely the main reason for the limited clinical response to PPI therapy in NERD patients. More than 45% of patients with functional heartburn reported insufficient control of heartburn after four weeks of treatment with omeprazole 20 mg once daily.15 Interestingly, in the same study, the authors demonstrated that in patients with NERD receiving omeprazole 20 mg daily, the higher the acid exposure in the distal oesophagus the greater the symptom response. Thus duration of distal oesophageal acid exposure appears to be a reliable predictive factor for response to PPI therapy. Functional esophageal disorders consist of a disease category that present with esophageal symptoms (heartburn, chest pain, dysphagia, globus) not explained by mechanical obstruction (stricture, tumor, eosinophilic esophagitis), major motor disorders (achalasia, EGJ outflow obstruction, absent contractility, distal esophageal spasm, jackhammer esophagus), or gastroesophageal reflux disease (GERD).
Dolan et al  found bone density to be reduced by up to 0.9 SD in individuals with EDS compared to healthy controls, but that study did not look at individuals with hEDS specifically. Compared to age- and sex-matched controls, Gulbahar et al  reported bone density reduction of up to 0.5 SD among premenopausal women with joint hypermobility syndrome (now considered identical to hEDS). However, Carbone et al  found no difference in bone density between women with hEDS and normal controls after adjusting for height, weight, and physical activity. Multiple other clinical features including (but not limited to) sleep disturbance, fatigue, postural orthostatic tachycardia, functional gastrointestinal disorders, dysautonomia, anxiety, and depression are associated with hEDS. Some of these features were formerly included as minor diagnostic criteria for hEDS [Beighton et al 1998].
The mechanisms responsible for pain, clinical characteristics, and the optimal therapeutic approach remain poorly understood. However, recent studies suggest that functional heartburn accounts for up to 50% of NERD patients and is an important contributor to the unpredictable response to antireflux therapy that has been observed in NERD patients. Due to the size of this patient subgroup and the complexity of the underlying mechanisms of their symptoms, further studies will be necessary in order to develop effective therapeutic modalities, which will probably not be limited to acid suppression. Hypermobility type Ehlers-Danlos syndrome (HT-EDS) is a relatively frequent, although misdiagnosed variant of Ehlers-Danlos syndrome commonly, mainly characterized by marked joint instability and mild cutaneous involvement. Chronic pain, asthenia, and gastrointestinal and pelvic dysfunction are characteristic additional manifestations.
Some patients were recruited with the help of Marfan Association UK. The questionnaires were completed by All patients by themselves, either in the Outpatients Department or at home, and returned them by post. Joint hyperextension may not need to be avoided. In a randomized controlled trial of physical therapy among 26 children and adolescents with joint hypermobility and knee pain, those allowed to exercise into hyperextension had similar improvement in pain score and better improvement in psychosocial score compared to those restricted to neutral joint position [Pacey et al 2013]. Depression is a common result of the chronic pain, disability, and other complications. Psychological and/or pain-oriented counseling can improve adaptation to and acceptance of these issues and
Clinical and genetic findings of selected patients based either on recognized clinical features or new pathogenic variants newly
Specific evidence based guidelines for GI symptoms in EDS patients do not exist, but there is recognition that precautions need to be taken for those undergoing surgery. Future studies are required to identify mechanisms leading to GI symptoms and more specific treatment guidelines are required. Despite significant advances in our knowledge of the mechanisms leading to gastro-oesophageal reflux, our understanding of the factors responsible for the symptoms associated with gastro-oesophageal reflux disease (GORD) remains limited.
Connective tissue is a supporting structure in our body and is made up of a number of proteins including collagen, which is the protein most often thought to be involved in EDS. Collagen is abundant in skin, ligaments and muscles where it gives these structures strength and support.
TLOSR, transient lower oesophageal sphincter relaxation; LOS, lower oesophageal sphincter. The emphasis on disease processes than symptoms has not spared the study of GORD rather.
Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic.
- Clinical variability is substantial.
- These symptoms are due to a sudden change in posture often, but sometimes occur after eating as well.
- Whilst the most common form of EDS is usually mild and often goes undiagnosed as a result, for some social people with EDS, symptoms can be severe.
- There is some preliminary research that suggests that people with hEDS are slightly more likely to have a small hiatus hernia at the lower end of the oesophagus.
They were excluded from the 2017 hEDS diagnostic criteria because they lack specificity for hEDS [Malfait et al 2017]. The diagnostic criteria for hEDS (and all other types of EDS) were revised by the International EDS Consortium in 2017 [Malfait et al 2017].
Problems with the automatically controlled (autonomic) bodily functions (including blood pressure and heart rate) were proposed to be a cause. Since then it has been shown that fast heart rate on standing (postural tachycardia syndrome, POTS) is associated with GI symptoms such as nausea, reflux, bloating, constipation, and diarrhea. Suggesting that hEDS, autonomic symptoms, and GI symptoms are indeed linked, though the exact mechanism is unknown. Other studies have confirmed that GI symptoms are common in patients with an existing diagnosis of hEDS.
Painful stimuli resulted in intense activation of the same areas and additional activation of the right anterior insular cortex and the anterior cingulate gyrus. The former is important in affective processing while the latter is important in pain processing and generating an affective and cognitive response to pain.56-58 In another study, Kern et al evaluated activation of cerebral cortical responses to oesophageal mucosal acid exposure using functional magnetic resonance imaging (FMRI).59 Ten healthy subjects underwent intra-oesophageal perfusion of 0.1 N hydrochloric acid over 10 minutes.
Hypermobility and Sleep
vEDS patients should wear a medical alert bracelet, necklace or similar. The EDS National Diagnostic Service has produced a medic alert sheet with the information that may be needed in case of an emergency. It is best to avoid invasive tests or invasive treatments unless strictly necessary, because of the risk of damage to skin and blood vessels.
It is certainly of note that the molecular diagnosis in the majority of the patients was achieved by direct Sanger sequencing of FKBP14 due to the strong suggestive clinical features. P5/FIV is the first child of healthy consanguineous first-cousin parents of Pakistani origin. He was born by emergency Cesarean section for fetal bradycardia, following spontaneous rupture of membranes and premature labor at 31 weeks gestation. On clinical examination he was noted to have a very wide cleft palate, mild micrognathia, and a large anterior fontanel.
The mechanisms responsible for pain, clinical characteristics, and the optimal therapeutic approach remain poorly understood. Response to potent antireflux treatment is relatively limited. Current and future treatment strategies for functional heartburn patients who have failed standard dose proton pump inhibitors (PPIs) include increased PPI dose in some, as well as addition of pain modulators in others. Fibromyalgia is a common diagnosis in people with JHS.
Such long delays and lack of understanding can lead to frustration (with doctors and with daily life), anger, anxiety, and depression. In summary, the review of the present patient cohort, the follow-up of three patients from our initial publication as well as the comparison with all published cases, reveals a quite consistent clinical presentation of the disorder and allows us to speculate on major and minor clinical criteria. In contrast to the broader clinical spectrum of phenotypic presentation in PLOD1-kEDS, FKBP14-kEDS thus far presents with a less pronounced phenotypical variability.