Diagnosis and treatment of the Ehlers-Danlos syndromes in China: synopsis of the first guidelines.

BACKGROUND: The Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders. EDS is clinically and genetically heterogeneous and usually involves multiple systems. There are 14 subtypes of EDS with hallmark features including joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical manifestations and their severity differ among the subtypes, encompassing recurrent joint dislocations, scoliosis, arterial aneurysm and dissection, and organ rupture. Challenges in diagnosis and management arise from the complexity of the disease, which is further complicated by its rarity. The development of clinical guidelines and implementation of coordinated multi-disciplinary team (MDT) approaches have emerged as global priorities. MAIN BODY: Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes was therefore established. Healthcare professionals were recruited from 25 top hospitals across China. The experts are specialized in 24 fields, including genetics, vascular surgery, dermatology, and orthopedics, as well as nursing care, rehabilitation, psychology, and nutrition. Based on GRADE methodology, the Guidelines were written by the Group supervised by methodologists, following a systemic review of all 4453 articles in PubMed published before August 9, 2023, using the search term "Ehlers Danlos". A coordinated MDT approach for the diagnosis and management of EDS is highly recommended by the Group, along with 29 specific recommendations addressing key clinical questions. In addition to the treatment plan, the Guidelines also emphasize integrating support from nursing care, rehabilitation, psychology, and nutrition. This integration not only facilitates recovery in hospital settings, but most importantly, the transition from an illness-defined life to a more "normalized" life. CONCLUSION: The first guidelines on EDS will shorten the diagnostic odyssey and solve the unmet medical needs of the patients. This article is a synopsis of the full guidelines.

The use and effectiveness of exercise for managing postural orthostatic tachycardia syndrome in young adults with joint hypermobility and related conditions: A scoping review.

PURPOSE: Postural Orthostatic Tachycardia Syndrome (POTS) is a form of dysautonomia. It may occur in isolation, but frequently co-exists in individuals with hypermobile variants of Ehlers-Danlos Syndrome (EDS) and related conditions (chronic fatigue syndrome [CFS] and fibromyalgia). Exercise is recommended for non-pharmacological POTS management but needs to be individualised. This scoping review explores the current literature on use and effectiveness of exercise-based management for POTS, with specific focus on individuals with joint hypermobility and related conditions who experience hypermobility, and/or pain, and/or fatigue. METHODS: A systematic search, to January 2023, of Medline, EMBASE, AMED, CINAHL and the Cochrane library was conducted. Studies that reported on adolescents and adults who had been diagnosed with POTS using standard criteria and underwent an exercise-based training intervention were included. RESULTS: Following full-text screening, 10 articles were identified (2 randomised control trials, 4 comparative studies and 4 case reports). One comparative study reported a small subset of participants with EDS and one case report included an individual diagnosed with CFS; the remainder investigated a wider POTS population. Overall, 3 months of endurance followed by resistance exercise, graduating from the horizontal-to-upright position reduced POTS symptoms and improved quality-of-life. CONCLUSION: The findings highlight a paucity of higher-level studies documenting exercise for POTS management in people with joint hypermobility and related conditions. Results from the wider POTS population demonstrate exercise is safe and effective. Large, well-designed clinical studies exploring exercise for POTS management adapting to meet the complex musculoskeletal and non-musculoskeletal features of symptomatic joint hypermobility are needed.

Prevalence and outcomes of select rare vascular conditions in females: A descriptive review.

Rare vascular conditions frequently pose a diagnostic and therapeutic dilemma for health care providers. Several of these conditions have distinct relevance to females populations but, due to their infrequency, there has been little reported on the outcomes of rare vascular conditions specifically in females populations. We performed a literature review of a selection of three rare vascular conditions known to either disproportionately affect females (median arcuate ligament syndrome and fibromuscular dysplasia) or have unique manifestations in females populations (vascular Ehlers-Danlos syndrome). We performed a descriptive review of the literature focused on these three vascular conditions and identified aspects of the current available research describing sex-based differences in prevalence, any pathophysiology explaining the observed sex-based differences, and the contribution of sex to outcomes for each disease process. In addition, considerations for pregnant females with respect to each rare vascular disease process are discussed.

Multidisciplinary chronic pain management strategies in patients with Ehlers-Danlos syndromes.

Ehlers-Danlos syndromes (EDS) are a group of disorders characterized by abnormal connective tissue affecting several organ systems. Patients with the hypermobile type of EDS (hEDS) commonly experience chronic pain which can present as musculoskeletal pain, fibromyalgia, neuropathic pain or abdominal pain. The effective management of chronic pain in hEDS patients is a challenge. This study reviews two cases of chronic pain in hEDS patients and the multimodal treatment regimen used along with peripheral nerve stimulation for shoulder and knee pains, never before reported in hEDS patients. Since hEDS associated chronic pain is multifactorial in origin, treatment requires a multidisciplinary approach which includes physical therapy, psychotherapy, pharmacotherapy and interventional pain procedures such as trigger point injections, peripheral nerve block, radiofrequency ablation and peripheral nerve stimulation.

Ehlers­Danlos Syndromes (EDS) are a group of disorders that affects the connective tissues that supports skin, muscles and organs. Patients with the hypermobile subtype of EDS (hEDS) often experience chronic pain of multiple locations including the muscles, joints, nerves, abdomen, head or generalized pain. Treating chronic pain in patients with hEDS is challenging. In this study, we review the treatment of chronic pain in two patients with hEDS using multiple therapies including the novel use of peripheral nerve stimulation in this patient population. Chronic pain in hEDS patients is caused by multiple different mechanisms and therefore, the treatment of this pain requires multiple different therapeutic interventions such as medications, physical therapy, psychotherapy and minimally invasive procedures such as peripheral nerve stimulation.

A Comprehensive Review: Chronic Pain Sequelae in the Presence of Ehlers-Danlos Syndrome.

PURPOSE OF REVIEW: Patients diagnosed with Ehlers-Danlos syndromes (EDS), and especially those with the hypermobility subtype, often experience a diverse range of acute and chronic pain conditions throughout their lifetime. These can present in a variety of different phenotypes and comorbidities, making it difficult to develop structured treatment protocols. This review seeks to summarize the current literature to address old and novel treatments for EDS. RECENT FINDINGS: Historically, medications and surgery have been used to treat patients with EDS but with low efficacy. Newer therapies that have shown promising effects for both decreasing pain and increasing quality of life include physical/occupational therapy, transcutaneous electrical nerve stimulation units, trigger point injections, low-dose naltrexone, and laser therapy. In addition, addressing the psychosocial aspects of pain with EDS through methods like cognitive behavioral therapy and patient education has shown to be vital in minimizing pain. Most research also emphasizes that pain management should not only focus on pain reduction, but on helping reduce symptoms of hypermobility, central sensitization, and fatigue to make an impactful difference. Research on pain in EDS is still limited with good clinical practice guidelines often limited by poor sample size and lack of clinical studies. Treatment options should be structured based on the specific type of pain pathology and presenting symptoms of each patient and their comorbidities. Future research should attempt to prioritize larger sample sizes, clear definitions of EDS subtypes, randomized trials for treatment efficacy, and more studies dedicated to non-musculoskeletal forms of pain.

Ehlers-Danlos Syndrome: An Analysis of the Current Treatment Options.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a multifaceted disease that can present with a variety of types of pain. Unfortunately, both the mechanisms and treatments for pain are poorly understood. The proposed treatments for the various musculoskeletal pain syndromes in EDS have had variable success, and it becomes much more imperative to better define and evaluate the current treatment modalities in treating this debilitating disease. OBJECTIVES: The purpose of this study was to investigate the currently available treatment modalities for patients with EDS and their efficacies in pain and symptom relief. STUDY DESIGN: Retrospective cohort study. SETTING: Institutional physical medicine and rehabilitation primary care clinic. METHODS: All patients were seen between January 2015 and April 2019, in which 98 patients with EDS were identified through retrospective chart review. Institutional review board approval was obtained, and all patients provided written consent to be included in the study. We reviewed various treatment modalities, including complimentary/alternative treatments, opioids/opioid-like medications, nonsteroidal antiinflammatory drugs, physical therapy, occupational therapy, muscle relaxants, neuropathic modulators, steroids, surgery/procedures, and acetaminophen. Treatment methods were extracted from individual patient charts, and efficacy was grouped into 3 categories: improvement, no effect, or worsened symptoms. RESULTS: The most common treatments used were complimentary/alternative treatments (n = 88). Occupational therapy and bracing were the most effective options with 70% of patients reporting improvement. Neuropathic modulators were the least well tolerated with 47% of patients reporting adverse effects. LIMITATIONS: Men were a small percentage of the study. Patients were not randomized, and pain score reporting was subjective. Patient data were extracted from a single practice setting. Timing and symptom onset were not measured. CONCLUSIONS: There is a relative paucity of published literature regarding the various treatment methods for EDS. Although our study is able to identify positive and negative trends with certain modalities, it is vital to understand that EDS is not a uniform diagnosis among patients, and that a combination of several different treatments usually is needed for optimal symptom control. Further research and investigation are necessary to develop a comprehensive treatment database for this complex condition. KEY WORDS: Ehlers-Danlos syndrome, pain, hypermobility, arthralgia, subluxation, genetic, physical therapy, interventional pain.

Management of Spontaneous Liver Hematoma in Ehlers-Danlos Syndrome Type IV: A Case Report.

INTRODUCTION: Liver hematoma is an uncommon feature of Ehlers-Danlos syndrome (EDS) type IV. The limited literature that exists to guide management does not establish a standard of care. CASE PRESENTATION: A 26-year-old man presented with acute abdominal pain caused by a large, spontaneous liver hematoma. Invasive prophylactic arterial embolization was done twice, but surgical evacuation was not offered because of concern for poor healing and brittle vasculature, later diagnosed as symptoms of the patient's EDS type IV. During hospitalization the patient died of spontaneous intracerebral and intra-abdominal hemorrhaging. CONCLUSION: This case illustrates a nonsurgical management option for spontaneous liver hematoma in a patient with EDS type IV. An interdisciplinary team should help guide care, including consideration of invasive procedures such as arterial embolization and surgery. Patient and family education, genetic testing, and timely medical record documentation may reduce the morbidity and mortality of patients with this syndrome.

Assessment of the Information Sources and Interest in Research Collaboration Among Individuals with Vascular Ehlers-Danlos Syndrome.

BACKGROUND: Patient-centered research requires active engagement of patients. The vascular Ehlers-Danlos Syndrome (vEDS) research collaborative was established to ascertain patient-centered vEDS research priorities and to engage affected individuals as research partners. Evaluation of access to information and interest in research among individuals with vEDS was the first step undertaken as part of this work. METHODS: A 28-question survey was created to evaluate 4 domains of interest: diagnostic and clinical care history, vEDS experience, information resources, and willingness to collaborate with researchers. The survey was created in REDCap™ and disseminated between January and April 2018 via the vEDS social media pages, blogs, and advocacy Web sites. Results were collated and described. A single open-ended question yielded additional narrative data, which were analyzed qualitatively. RESULTS: Of the 300 responses, 228 (76%) were completed on behalf of oneself. The vEDS diagnosis was confirmed by genetic testing for 85% of respondents. When asked "Did a physician explain vEDS to you and how to manage it?" 25% answered no. Most had a primary care provider (65%), cardiologist (56%), and vascular surgeon (52%). Only 32% had a local vascular surgeon. The most commonly reported frustration was no cure/treatment available and the emergency rooms do not know what VEDS is (64.5% and 61.8%, respectively). The Internet was the most useful information source (62.3%) followed by a geneticist (18.4%). Most (87.7%) are willing to share their medical records for research studies (87.7%) and wished to be contacted about future studies (83.8%); however, only 65.4% would be willing to upload medical records via a secure confidential Web application. The most common reason for interest in research partnership was to advance research for a treatment/cure (83.8%) and helping others learn from their experiences (82.9%). The qualitative analysis provided additional insights into the patient experience living with vEDS. CONCLUSIONS: Among individuals with vEDS, there is substantial frustration with the lack of treatment, lack of knowledge among health care providers, and a high degree of interest in research involvement. The survey highlights an opportunity to discuss the optimal modality for research participation and methodologies for building trust in the research teams. The methodology lessons learned can also be applied to other rare vascular diseases.

Síndrome de Ehlers-Danlos hipermóvel: um relato de caso / Hypermobile Ehlers-Danlos syndrome: a case report

A síndrome de Ehlers-Danlos é estabelecida por distúrbios hereditários do tecido conjuntivo que tem como manifestações principais a hipermobilidade articular, a hiperextensibilidade da pele e a fragilidade de tecidos, como articulações, ligamentos, pele, vasos sanguíneos e órgãos internos. São reconhecidos 13 subtipos, de acordo com Classificação Internacional de 2017. Dentre estes, abordamos o hipermóvel, cujo diagnóstico é eminentemente clínico, com manifestações sistêmicas distintas. Esse artigo refere-se ao caso de uma paciente diagnosticada com síndrome de Ehlers-Danlos hipermóvel, tendo como intuito a atualização acerca dos novos critérios diagnósticos, assim como o diagnóstico precoce de tal raropatia.

Ehlers-Danlos syndrome is established through hereditary disorders of connective tissue, and has as its manifestations: joint hypermobility, skin hyperextensibility, and fragility of tissues such as joints, ligaments, skin, blood vessels, and internal organs. Thirteen subtypes have been recognized according to the 2017 International Classification. Among these, the hypermobile type, the diagnosis of which is eminently clinical, with distinct systemic manifestations, will be addressed. This article refers to the case of a patient diagnosed with hypermobile Ehlers-Danlos syndrome, with the objective of updating the new diagnostic criteria, as well as the early diagnosis of such a rare disease.

A Novel Frameshift COL3A1 Variant in Vascular Ehlers-Danlos Syndrome.

Ehlers-Danlos syndromes (EDSs) are a group of heritable connective tissue disorders with distinct genetic etiologies. Of the 13 currently recognized types of EDS, the vascular type EDS (vEDS) is generally considered the most severe and is associated with a decreased life expectancy due to spontaneous arterial, intestinal, and or uterine rupture. Diagnosis of vEDS is supported by genetic testing confirming the presence of pathogenic variations in COL3A1, a type III procollagen gene. Management of vEDS is usually conservative with control of hemodynamic stress, frequent cardiovascular imaging, and, if indicated, a thoughtful endovascular intervention or surgical repair. We present a novel frameshift variant in COL3A1 leading to vEDS with multiple vascular involvements. Based on our literature review, this variant has not been reported and may result in a less severe form of vEDS. Our case report provides insight into genetic variants and clinical expression of vEDS.

Recognizing and Effectively Managing Hypermobility-Related Conditions.

Hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) can cause widespread or chronic pain, fatigue, and proprioceptive and coordination deficits resulting in functional restrictions. These conditions are common and often unrecognized, and patients are likely to present in physical therapy for musculoskeletal injuries, pain, or coordination deficits. Although physical therapy is considered central to managing these conditions, many patients report pain and iatrogenic injuries due to inappropriate interventions. The diagnostic classification for these conditions was revised in 2017 to supersede previous diagnostic categories of Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome-hypermobility type/type III. It is now known that these conditions affect multiple body systems and not just joints and that patients require a holistic approach. This Perspective article will describe the 2017 diagnostic classification system, clinical presentation, examination, evaluation, and management of patients with HSD/hEDS. Both adult and pediatric cases are presented to illustrate the patient management concepts discussed. This knowledge can lead to more effective management of this patient population.

Spinal fluid evacuation may provide temporary relief for patients with unexplained widespread pain and fibromyalgia.

Fibromyalgia (FM) exhibits characteristics of a neurological disorder, and similarities have been identified between FM and idiopathic intracranial hypertension (IICH). When intracranial pressure rises, the drainage of excess cerebrospinal fluid (CSF) through the subarachnoid space of the cranial and spinal nerves increases. Higher CSF pressure irritates nerve fibers inside nerve root sheaths and may consequently cause radicular pain, as was reported in patients with IICH. Moreover, the cut-off of 20-25 cm H20 used to define IICH may be too high, as has been suggested in patients with chronic fatigue syndrome. We hypothesize that the neurological symptoms of FM are caused by the dysregulation of cerebrospinal pressure (CSP) and that spinal fluid drainage can relieve this pain. Exploring the processes underlying increased CSP may provide an alternative explanation for the generation of unexplained widespread pain (WSP) and FM as opposed to central sensitization. Additionally, when performing a lumbar puncture for diagnostic reasons, it is useful to measure opening pressure in patients with chronic WSP.

Successful treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV without arterial puncture: the transvenous triple-overlay embolization (TAILOREd) technique.

We report successful transvenous treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV using a novel triple-overlay embolization (TAILOREd) technique without the need for arterial puncture, which is known to be highly risky in this patient group. The TAILOREd technique allowed for successful treatment using preoperative MR angiography as a three-dimensional overlay roadmap combined with cone beam CT and live fluoroscopy, precluding the need for an arterial puncture.

Pain management in the Ehlers-Danlos syndromes.

Chronic pain in the Ehlers-Danlos syndromes (EDS) is common and may be severe. According to one study, nearly 90% of patients report some form of chronic pain. Pain, which is often one of the first symptoms to occur, may be widespread or localized to one region such as an arm or a leg. Studies on treatment modalities are few and insufficient to guide management. The following is a discussion of the evidence regarding the underlying mechanisms of pain in EDS. The causes of pain in this condition are multifactorial and include joint subluxations and dislocations, previous surgery, muscle weakness, proprioceptive disorders, and vertebral instability. Affected persons may also present with generalized body pain, fatigue, headaches, gastrointestinal pain, temporomandibular joint pain, dysmenorrhea, and vulvodynia. Pain management strategies may be focused around treating the cause of the pain (e.g., dislocation of a joint, proprioceptive disorder) and minimizing the sensation of pain. Management strategies for chronic pain in EDS includes physical therapy, medications, as well as durable medical equipment such as cushions, compressive garments, and braces. The different modalities are discussed in this paper. © 2017 Wiley Periodicals, Inc.

A New COL3A1 Mutation in Ehlers-Danlos Syndrome Vascular Type With Different Phenotypes in the Same Family.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe connective tissue disorder caused by mutations in the collagen type III alpha I chain ( COL3A1) gene. We describe a pathogenetic heterozygous COL3A1 mutation c.3140 G>A, p. Gly1047Asp, identified using next-generation sequencing, in a 40-year-old Italian female. The genetic test performed on her relatives, which present different clinical phenotypes, confirmed that they carry the same mutation in heterozygous state. This finding confirms that mutations causing vEDS have an incomplete penetrance.

[Not Available]. / Ehlers-Danlos-Tschernogobow : Histoire contrarlée de la maladie.

Ehlers-Danlos disease had a paradoxical fate. Clinically identified 123 years ago, it is unknown to nearly all present doctors. Often described for its dramatic aspects, diagnostic confusion with fibromyalgia in particular, ignorance of effective treatments such as oxygen therapy and orthotics are new concepts that should shake the prejudices derived from the history of this disease.

Síndrome de Ehlers-Danlos vascular: complicaciones vasculares graves en enfermos con hipermovilidad articular / Vascular Ehlers-Danlos syndrome: severe vascular complications in patients with articular hypermobility

El Síndrome de Ehlers-Danlos Vascular es una de las Alteraciones Hereditarias del Tejido Conectivo. Es poco frecuente, pero es de alta morbilidad y mortalidad. Se debe a una mutación del gen COL3A1, que da debilidad del tejido colágeno, por lo que se pueden producir complicaciones graves afectando a la piel, tubo digestivo, hígado, pulmón y sistema vascular. Se pueden producir rupturas intestinales, neumotórax espontáneo, dilatación o ruptura aortica y anuerismas, lo que puede llevar a la muerte súbita del paciente.

The Vascular Ehlers-Danlos is one of Hereditary Diseases of Connective Tissue. Has low prevalence, but high morbidity and mortality. It is due to a COL3A1 gene mutation, producing tissue fragility, which can produce serious complications in the skin, digestive tract, liver, lungs and in the vascular system. It is frequently associated to intestinal ruptures, spontaneous pneumothorax, dilation or rupture of the aorta anuerism, which can lead to sudden death.

Síndrome de Ehlers-Danlos Clásico o Ehlers-Danlos tipo I - II / The Classic Ehlers-Danlos or Ehlers-Danlos type I - II

El Síndrome de Ehlers-Danlos Clásico o Ehlers-Danlos tipo I - II, al igual que el Ehlers-Danlos Vascular son poco frecuentes, si se les compara con el tipo Hipermovible o tipo III, el que afecta al 39 por ciento de la población chilena. Es importante porque al tener marcada hiperlaxitud articular (contorsionistas) presenta subluxaciones importantes. Además, debido a la gran hiperextensibilidad de la piel, la que es muy frágil, tiene tendencia a heridas y a mala cicatrización. Al igual que los otros tipos de Síndrome de Ehlers-Danlos, el Clásico puede tener Hábito Marfanoide o/y Disautonomía. Se puede presentar también con Osteopenia u Osteoporosis, hernias, várices, hemorroides y prolapso. Tiene herencia autosómica dominante y la alteración genética es conocida (COL5A1 o COL5A2).

The Classic Ehlers-Danlos or Ehlers Danlos type I - II, as the Vascular Ehlers-Danlos are infrequent, as compared with the Hypermobile or type III, that affects 39 percent of the chilean population. It is important because due to the marked joint hypermobility (contosionists) presents important subluxations. Also due to the important skin laxity, which is fragile it has tendency to injuries and poor cicatrization. As the other Ehlers-Danlos types, the Classic Ehlers-Danlos can present with Marfanoid habitus and or Dysautonomia. It also can have Osteopenia or Osteoporosis, hernias, varicose veins, hemorrhoids and prolapse. It has dominant Autosomic inheritance and the genetic alteration is known (COL5A1 or COL5A2).

Aggressive change of a carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV.

The authors report a rare case of a carotid-cavernous fistula (CCF) secondary to Ehlers-Danlos syndrome (EDS) type IV which showed an aggressive angiographical change.A 59-year-old woman presented with headache, right pulsatile tinnitus, and diplopia on the right side. The diagnostic angiography demonstrated a right CCF. Accordingly transarterial embolization of the fistula was attempted 5 days later. The initial right internal carotid angiography showed an aneurysm on the petrous portion of the internal carotid artery (ICA) which was not recognized in the diagnostic angiography. Spontaneous reduction of the shunt flow and long dissection of the ICA were also revealed. The aneurysm was successfully occluded with coils, and only minor shunt flow was shown on the final angiogram. EDS type IV was diagnosed with a skin biopsy for a collagen abnormality. After the operation, the stenosis of the right ICA gradually progressed, although there was no recurrence of the CCF.Interventional treatment for patients with EDS can cause devastating vascular complication. We should be aware of the possibility of EDS type IV when a spontaneous CCF shows unusual angiographical change because early diagnosis of EDS type IV is crucial for determination of the optimum treatment option.

Postural orthostatic tachycardia syndrome (POTS): association with Ehlers-Danlos syndrome and orthopaedic considerations.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is the most common of several types of dysautonomia, characterized by dysfunction of the autonomic nervous system manifesting with symptoms of orthostatic intolerance with or without associated orthostatic hypotension and excessive autonomic excitation. Given the numerous presenting musculoskeletal symptoms of POTS and its known associations with other clinical entities like Ehlers-Danlos syndrome, POTS constitutes an unusual treatment challenge of which the orthopaedic surgeon and other related healthcare providers should be aware. CASE DESCRIPTION: We describe two patients with a diagnosis of POTS and musculoskeletal manifestations. The first is a 13-year-old boy with a concurrent diagnosis of Ehlers-Danlos syndrome and worsening back pain. The patient had resolution of his musculoskeletal symptoms after treatment with a Boston Overlap LSO brace and physical therapy and resolution of his cardiovascular symptoms after pharmacologic treatment. The second patient is a 17-year-old girl with an L1 vertebral hemangioma and pain of sudden onset radiating to her lower extremities. Her symptoms were controlled with therapy and gabapentin. LITERATURE REVIEW: POTS is a poorly understood and controversial clinical entity with lack of awareness and knowledge regarding the syndrome by the majority of medical specialists. Its complex and wide range of clinical presentation has led to being commonly mistaken with malingering, depression and anxiety disorders. Review of the literature did not yield any previous studies addressing POTS and the special considerations for the orthopaedic surgeon caring for these patients; previous studies of large patient series focus on investigating the pathologic substrate of POTS and the efficacy of various treatment modalities on the cardiovascular dysregulation. CLINICAL RELEVANCE: These two cases show that understanding and knowledge of this syndrome and its comorbidities should guide any diagnostic approach or therapeutic intervention by the orthopaedic surgeon caring for patients with this syndrome. It is important that the surgeon is aware of the benefits of detailed patient education and physical conditioning, the increased perioperative complications, and the need for specialized anesthesia.