INTRODUCTION — The hypermobile subtype of Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) are among a group of conditions characterized by joint hypermobility and other frequently shared clinical features (table 1). Many of the patients with hEDS and HSD were historically described as having joint hypermobility syndrome (JHS), a term no longer used to classify patients since a major revision of the criteria for JHS and the Ehlers-Danlos syndromes (EDS) in 2017 [1,2].
HSD includes those individuals with a hypermobility-related condition who do not fulfill either the more stringent criteria for hEDS or criteria for another of the hereditary disorders of connective tissue (HDCT) [3,4].
An overview of the epidemiology, pathogenesis, clinical manifestations, and diagnosis of hEDS and HSD in adults and in younger persons is presented here. The management of these conditions is described separately. (See "Treatment and prognosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder".)
Overviews of the clinical manifestations, diagnosis, and management of the other, rarer subtypes of EDS; the clinical manifestations and treatment of Marfan syndrome and Loeys-Dietz syndrome and other related disorders; osteogenesis imperfecta; and Stickler syndrome are also presented separately. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes" and "Overview of the management of Ehlers-Danlos syndromes" and "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Osteogenesis imperfecta: An overview" and "Syndromes with craniofacial abnormalities", section on 'Stickler and Marshall syndromes'.)
TERMINOLOGY — The nomenclature for conditions characterized by joint hypermobility has evolved in an effort to better describe different patient populations (table 1); in 2017, terminology for joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome (EDS) was updated by an international committee of experts in this subject [1,2].
Joint hypermobility is also a common feature of many of the genetically and phenotypically defined hereditary disorders of connective tissue (HDCT), which include the various subtypes of EDS, Marfan syndrome, Loeys-Dietz syndrome, and Stickler syndrome, among others.
The hypermobile type of EDS (hEDS) and hypermobility spectrum disorder (HSD) are defined as follows:
●Hypermobile Ehlers-Danlos syndrome – The 2017 international criteria include revised diagnostic criteria for hEDS [2] (table 2). (See 'The 2017 international criteria for the diagnosis of hEDS' below.)
●Hypermobility spectrum disorder – The term HSD is now used to describe those individuals with a symptomatic hypermobility-related condition who do not fulfill either the comparatively more stringent criteria for hEDS, which generally include involvement of at least one other body system; or criteria for another of the HDCTs [3,4]. Notably, for patients with HSD, the term "spectrum" is used to highlight the variety of phenotypic patterns of disease presentations that can arise in this group, but it is not intended to suggest a scale of severity of symptoms.
In clinical practice, people living with HSD and hEDS often have similar concerns, whether musculoskeletal, visceral, autonomic, anxiety-related, or others, and these issues were reviewed in detail by the international consortium in a series of reports [5].
The now outdated term, JHS, which was used before the 2017 update to describe the condition of generalized joint hypermobility among individuals also experiencing related symptoms, will be used in this topic review where pre-2017 descriptions or criteria for JHS were used to define patients for inclusion in studies.
EPIDEMIOLOGY — Joint hypermobility is common, with up to one in five individuals in the general population having localized or generalized hypermobility [6]. At this frequency, joint hypermobility can be considered a physical trait rather than a disorder. Symptomatic, disabling, hypermobility-related conditions are less common at approximately 1 in 500 of the general population [7].
Hypermobility spectrum disorder (HSD) is common in musculoskeletal disease clinics, but the diagnosis is often missed. The actual prevalence of these conditions is not known. Data on joint hypermobility syndrome (JHS), which since the 2017 criteria would be segregated into either HSD or hypermobile Ehlers-Danlos syndrome (hEDS), showed JHS to be a common presentation in the rheumatology clinic [8,9]. In one large, general population survey in the United Kingdom, the combination of joint hypermobility and chronic widespread pain, which is typical of many patients with hypermobility-related disorders, was found in 3 percent of the surveyed individuals [10].
There has been a relative paucity of general population studies or other studies of sufficient sample size to accurately estimate the prevalence of JHS [11]. However, in 2019, a national survey in Wales, based upon diagnostic coding in health records for primary care and hospital admissions, described a population prevalence of JHS, combined with all types of Ehlers-Danlos syndromes (EDS), to be approximately 1 in 500 [7].
Joint hypermobility alone is common in the general population, affecting approximately 10 to 20 percent of individuals to some degree; it may be present either in isolated joints or be more generalized throughout the body [6]. It is more common in childhood and adolescence, in females, and in Asians and West Africans. Joint hypermobility tends to lessen with age and has strong heritability. In population-based data, joint hypermobility decreases throughout the lifespan and is more common in females at all ages [6,12].
NATURAL HISTORY — Individuals with hypermobility-related conditions such as hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) may develop recurrent soft tissue injuries, fatigue, chronic regional or widespread pain, declining physical capacity, anxiety states, and a number of systemic concerns, including autonomic cardiovascular and bowel dysfunction. All these concerns can have a major impact on activities of daily living and quality of life in people with hEDS or HSD if not remedied (series of reports, [5]).
PATHOPHYSIOLOGY — The pathophysiologic basis of hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) is not fully understood. No structural abnormality in collagen or related proteins or in the genes encoding such molecules has yet been identified, but research to identify potential genetic markers within populations of people with hEDS is ongoing.
The pattern of occurrence of HSD or hEDS in families is generally consistent with dominant inheritance, but the penetrance of signs and symptoms is highly variable among family members. Detailed family studies have identified multiple pedigrees in which HSD, hEDS, or both segregated as a single dominant trait with incomplete penetrance and variable expression [13].
The lack of a well-defined biologic marker in HSD and hEDS contrasts with most other hereditary disorders of connective tissue (HDCT), including other forms of Ehlers-Danlos syndrome (EDS) and Marfan syndrome, for which abnormalities in collagen and fibrillin biology and associated genetic mutations are well documented. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes", section on 'Genetics and pathogenesis' and "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders", section on 'Genetics'.)
Abnormalities that appear either unrelated or only indirectly related to connective tissue abnormalities have also been identified in patients with hypermobility and may contribute to the pathogenesis of the clinical syndrome.
These include:
●Poor proprioception – Reduced proprioception has been associated with joint hypermobility [14].
●Pain – Pain in hEDS and HSD is multifactorial; it may arise as a consequence of recurrent soft tissue injuries, dislocations, and nerve entrapment, and through neuropathic mechanisms of central and peripheral sensitization [15,16].
●Fatigue – Fatigue is most likely a manifestation of chronic pain and poor sleep due to pain and may also occur as a symptom of autonomic dysfunction [17].
●Autonomic dysfunction and related conditions – There is a strong association of JHS with cardiovascular autonomic dysfunction [18,19], bowel anatomic and autonomic dysfunction [20-24], and bladder dysfunction [25,26].
●Anxiety – Anxiety states, which are over-represented in these patients, may have a genetic linkage in approximately 15 percent of such patients. The observed prevalence of anxiety is higher than pain; the basis for this is not fully understood. One factor may be the concerns of patients regarding the multiple comorbidities associated with joint hypermobility for which the relationship with HSD and hEDS is often not appreciated [27-30].
CLINICAL MANIFESTATIONS — The major clinical features of both hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) include symptoms and findings related to the musculoskeletal changes, including joint hypermobility (picture 1A-D).
In hEDS, there is also fragility of skin and supportive connective tissues and some features common to other hereditary disorders of connective tissue (HDCT), although the severity of these latter manifestations varies between the different disorders [2].
Additionally, systemic features, including chronic widespread pain, fatigue, autonomic dysfunction, and gastrointestinal dysmotility, are often present in patients with HSD or hEDS, which exhibits a complex spectrum of signs and symptoms of varying degrees and combinations.
Patients may present with any combination of the following [2]:
●Musculoskeletal manifestations – These may include:
•Recurrent joint sprains and ligament and tendon injuries.
•Mechanical pain related to biomechanical differences, especially in the lower limbs.
•Persistent chronic pain in one or many joints.
•Complex widespread musculoskeletal pain with evidence of central sensitization and neuropathic qualities. (See "Overview of chronic widespread (centralized) pain in the rheumatic diseases".)
•Episodes of recurrent joint instability, including subluxations (incomplete dislocation) or dislocations. Dislocations often arise from minor trauma. The more commonly affected joints include the carpometacarpal joint at the thumb, and the shoulder, hip, and ankle. The patellar ligament may be so lax as to allow the patella to displace laterally or medially. Less often, some individuals dislocate joints by minor self-manipulation.
•Poor proprioception, coordination difficulties, and loss of balance.
•Features of the Marfanoid body habitus (a range of skeletal disproportions associated with increased length and decreased breadth of long bones) (table 3). (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders", section on 'Skeletal findings'.)
●Skin and other tissue manifestations in hypermobile Ehlers-Danlos syndrome – These include:
•Hyperextensible skin (picture 2), the texture of which is usually soft and velvety/silky. In children, significant skin transparency would need referral for genetic evaluation.
•Easy bruising.
•Wide, paper-thin scars, not "atrophic" like those seen in rarer classical type of Ehlers-Danlos syndrome (EDS).
•Multiple stretch marks (striae atrophicae), typically arising during the adolescent growth spurt.
•Recurrent abdominal wall hernias.
•Pelvic floor weakness with rectal and/or vaginal prolapse, and bladder dysfunction (dysuria, urgency, frequency, urge, and stress incontinence).
●Other conditions – Other disorders often associated with HSD and hEDS include:
•Gastrointestinal and genitourinary (including gynecologic; 50 percent of symptomatic patients):
-Bowel symptoms suggestive of functional gastrointestinal disorders (constipation alternating with diarrhea, bloating, nausea, and pain) and early satiety.
-Bowel dysmotility, especially slow-transit constipation.
-Heavy and painful menstrual bleeding.
•Disabling, persistent fatigue.
•Anxiety, depression, and phobia (eg, fear of movement).
•Autonomic dysfunction:
-Palpitations, chest pain, and near-syncope or syncope due to postural tachycardia.
-Orthostatic symptoms, including (near) blackouts due to postural hypotension.
-Skin color changes, abnormal sweating.
DIAGNOSIS
Indications for diagnostic evaluation — Patients with clinical manifestations suggestive of hypermobility spectrum disorder (HSD) or hypermobile Ehlers-Danlos syndrome (hEDS) (see 'Clinical manifestations' above) should undergo a diagnostic evaluation, including ascertainment of their degree of joint hypermobility on physical examination, using the Beighton hypermobility score (table 4) (see 'Beighton score for joint hypermobility' below), as well as assessment for historical evidence of joint hypermobility.
The presence of generalized joint hypermobility, including its presence historically, may be suspected in adult patients over the age of 18 years who answer "yes" to two or more questions in a simple five-part questionnaire (table 5) [31]:
●Can you now (or could you ever) place your hands flat on the floor without bending your knees?
●Can you now (or could you ever) bend your thumb to touch your forearm?
●As a child did you amuse your friends by contorting your body into strange shapes or could you do splits?
●As a child or teenager did your shoulder or kneecap dislocate on more than one occasion?
●Do you consider yourself double-jointed?
The 2017 international criteria for the diagnosis of hEDS — The diagnosis of hypermobile Ehlers-Danlos syndrome (hEDS) can be made clinically, based upon the medical history and physical examination, using the 2017 international criteria (table 2) [2]. The criteria describe the combinations of musculoskeletal and other historical and clinical findings that may be used to make the diagnosis.
hEDS is diagnosed if an individual fulfills:
●Criterion 1 – Presence of generalized joint hypermobility.
●Criterion 2 – At least two of sections A, B, and C in criterion 2 (other tissue signs, family history, and joint pain or joint instability).
●Criterion 3 – The absence of another hereditary disorder of connective tissue (HDCT) or other cause for relevant signs or symptoms found. (See 'Features suggesting an alternative diagnosis' below and 'Differential diagnosis' below.)
The criteria include use of the Beighton hypermobility score (table 4) to define joint hypermobility (see 'Beighton score for joint hypermobility' below) and the five-part hypermobility questionnaire (table 5) [31].
There are currently no diagnostic laboratory tests (eg, blood tests, molecular genetic analyses, imaging, or histopathology) for hEDS.
Hypermobility spectrum disorder — A diagnosis of HSD is made in the presence of the same musculoskeletal concerns as seen in hEDS, but the absence of sufficient additional features to make a diagnosis of hEDS or other HDCT or another primary cause for joint instability, such as a myopathy, neuropathy, or a bone dysplasia (see 'Features suggesting an alternative diagnosis' below and 'Differential diagnosis' below). In patients with HSD, the distribution of hypermobility can be generalized, local/regional, or peripheral (small joints), while in hEDS, the criteria require the hypermobility to be generalized (table 6) [3,4].
Beighton score for joint hypermobility — Joint hypermobility is ascertained by determination of the Beighton score, except in children younger than three. The score depends upon the presence of joint hypermobility in the hands, elbows, lumbar spine, and knees using specific examination techniques (table 4) [32]. One point is awarded for the ability to perform each of nine maneuvers (including four maneuvers tested bilaterally and evaluation of the spine).
The score is not appropriate for use in children younger than three, as they have not yet fully ossified their epiphyses; consequently, all of these children have excessive ranges of motion at the joints. The 2017 Ehlers-Danlos syndrome (EDS) criteria use different cutoff points on the Beighton Score for joint hypermobility for different age groups [3]. (See 'The 2017 international criteria for the diagnosis of hEDS' above.)
The specific maneuvers used to obtain a Beighton score include:
●Passive apposition of the thumb to the volar aspect of the ipsilateral forearm
●Passive hyperextension of fingers, demonstrated by passive dorsiflexion of the fifth metacarpophalangeal joint to at least 90 degrees
●Hyperextension of the elbow to at least 10 degrees
●Hyperextension of the knee to at least 10 degrees
●Flexion of the spine with placement of the palms flat on the floor without bending the knees
Scores need to be assessed in the context of age- and sex-matched norms. For the 2017 criteria, a score of ≥6 identifies generalized joint hypermobility in children, ≥5 in adolescents and younger adults, and ≥4 in adults aged 50 years and over. According to an analysis of population data, use of these definitions may still fail to identify males with unusually high levels of joint hypermobility while overdiagnosing young females as having joint hypermobility [12].
The presence of joint hypermobility can be documented by an examination limited to those areas required for calculating the Beighton score, but an examination for joint hypermobility and joint stability that is adequate for fuller assessment of the patient and the formulation of treatment plans should also encompass the other joints, including any symptomatic joint as well as the temporomandibular joints, shoulders, hips, cervical and thoracic spine, ankles, and feet. Supplemental clinical assessment tools for the upper limb (Upper Limb Hypermobility Assessment Tool [ULHAT]), lower limb (Lower Limb Assessment Score [LLAS]), and foot (Foot Posture Index [FPI]) are now available [33-35].
Features suggesting an alternative diagnosis — Because of the lack of definitive diagnostic tests for hEDS and HSD and the potential for serious complications from disorders that may resemble these conditions (see 'Differential diagnosis' below), some patients will benefit from evaluation by an expert in medical genetics to exclude another disorder before establishing a firm diagnosis. The presence of any of the following features would suggest a need for such a referral:
●Extensive widened atrophic scars
●Significant sagging skin
●Premature aged appearance
●Severe periodontal disease
●Severe corneal thinning, retinal detachment
●Significant kyphoscoliosis
●History of organ rupture
●Young-onset unexplained aortic root dilation, arterial dissection, or aneurysm
●Hand and foot deformities
●Unexplained significant or extensive varicosities at a young age
●Recurrent large hernias
●Recurrent pneumothoraces
●Hypertelorism (wide-set eyes), bifid uvula, or cleft palate
●Intellectual disability
DIFFERENTIAL DIAGNOSIS — The differential diagnosis for hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) includes the conditions that have generalized joint hypermobility as a clinical feature, particularly Marfan syndrome and other types of the Ehlers-Danlos syndromes (EDS). A variety of clinical features may suggest the possibility of another, potentially serious, disorder and the need for evaluation by an expert in medical genetics (see 'Features suggesting an alternative diagnosis' above). Marfan syndrome is the principal diagnosis to exclude, although there are a number of conditions that may be associated with joint hypermobility [36]. Of particular importance are:
●Joint hypermobility – Patients with joint hypermobility alone can be distinguished from HSD and hEDS by the absence of additional symptoms and findings. (See 'Diagnosis' above.)
●Marfan syndrome – Joint hypermobility and the marfanoid habitus (table 3) are features of Marfan syndrome. Other features of Marfan syndrome, including scoliosis, kyphosis, dilatation of the aortic root and aortic arch, aortic dissection, ectopia lentis, or dural ectasia, may help to distinguish the disorders. Additional study may be required in patients in whom this distinction is uncertain based upon clinical grounds alone, such as ophthalmologic consultation, echocardiography, and gene testing for causes of vasculopathy. There are many Marfan-like conditions that are rare and have similar features to Marfan [37]. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders".)
●Loeys-Dietz syndrome – Loeys-Dietz syndrome is an important group of autosomal dominant conditions that may present with joint hypermobility but also exhibit major cardiovascular involvement, with aortic aneurysms and arterial tortuosity; hence, it is very important to consider these in the differential diagnosis. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders", section on 'TGFBR1 or TGFBR2 mutation: Loeys-Dietz syndrome'.)
Loeys-Dietz syndrome can generally be distinguished from hEDS and HSD by clinical features and genetic testing; clinical features that may suggest one of the subtypes of this syndrome and indicate a need for referral and genetic testing include [38]:
•The triad of hypertelorism, cleft palate, or bifid uvula, and arterial tortuosity or aneurysm.
•Early-onset aortic aneurysm often combined with joint hypermobility and other skeletal abnormalities, and/or blue sclerae, thin skin with atrophic scars, easy bruising, bicuspid aortic valve, patent ductus arteriosus, or cardiac septal defects.
•Aortic root dilatation and dissection, familial (autosomal dominant) thoracic aortic aneurysms, and early-onset aortic or arterial dissection.
•Marfan syndrome-like phenotype (not meeting criteria for Marfan syndrome).
•Features similar to EDS-vascular type but with negative biochemical and genetic testing for this condition. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes", section on 'Vascular EDS'.)
●Ehlers-Danlos syndromes – EDS are a group of conditions generally characterized by hyperelasticity and fragility of the skin and by hypermobility of the joints. In patients with more florid skin abnormalities (eg, atrophic scarring or marked hyperextensibility or fragility) or severe scoliosis, or when there is a strong family history of easy bleeding, including hematoma, or vascular collapse, the rarer variants of EDS, including classical EDS and vascular EDS, should be considered [2]. The diagnosis of EDS, other than hEDS, may be made clinically and confirmed or excluded by genetic testing or by analysis of collagen obtained from cultured fibroblasts following skin biopsy. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes", section on 'Clinical manifestations and diagnosis'.)
Other conditions with widespread or localized musculoskeletal pain (eg, fibromyalgia, injuries of tendons and ligaments) can usually be distinguished from hEDS and HSD by the lack of generalized joint hypermobility and by the presence of features suggesting these conditions on the medical history and examination.
SUPPLEMENTAL AND POSTDIAGNOSTIC EVALUATION — Additional testing may be required to either help establish the diagnosis (eg, by excluding other conditions) or to further characterize symptoms or abnormal findings identified in the history and physical examination; testing depends upon the specific clinical findings. Screening blood tests are not required in the absence of clinical features suggesting a disorder other than or in addition to hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD).
Indications for testing depend upon the clinical presentation and may include:
●Joint symptoms and findings other than hypermobility – Imaging of affected regions of the musculoskeletal system in patients suspected of degenerative joint changes, subluxation, dislocation, or a congenital anatomic defect. Imaging studies may demonstrate degenerative disease, vertebral listhesis, or joint subluxation. Static images may appear normal. Thus, dynamic ultrasound and weightbearing images with joints placed in extreme ranges of movement may be more informative.
In patients with height less than the third percentile, a radiographic skeletal survey may be needed to rule out skeletal dysplasia. (See "Skeletal dysplasias: Approach to evaluation".)
●Symptoms of developmental disability – In pediatric patients with comorbid intellectual disability, significant attentional or specific learning difficulties (developmental coordination disorder, language difficulties), or additional congenital anomalies, a workup for developmental disability should be undertaken, including a comparative genomic hybridization (CGH) array. Generalized joint hypermobility and/or joint laxity is associated with many chromosomal conditions, including duplications and deletions, and some syndromes (eg, Kabuki, trisomy 21) have joint hypermobility and laxity as a feature. Referral to a clinical geneticist for full evaluation is recommended for any patient with severe developmental delay or learning disability before making a diagnosis of HSD. (See "Developmental-behavioral surveillance and screening in primary care" and "Down syndrome: Clinical features and diagnosis".)
●Suspected cardiac or aortic disease – In patients with a heart murmur, those in whom Marfan syndrome or Marfan-like disorder or Loeys-Dietz syndrome is suspected, and children with dysmorphology or nonmusculoskeletal anomalies, echocardiography should be performed to determine if congenital cardiac disease, mitral valve disease, or abnormalities of the aorta or aortic valve are present. (See "Mitral valve prolapse: Clinical manifestations and diagnosis" and "Clinical manifestations and diagnosis of thoracic aortic aneurysm" and "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders", section on 'Aortic disease' and "Clinical manifestations and diagnosis of chronic aortic regurgitation in adults".)
●Suspected low bone mass – Patients with a personal history of low-trauma fracture or pediatric patients with a family history of early osteoporosis should undergo bone mineral density testing to determine if osteopenia or osteoporosis is present. (See "Screening for osteoporosis in postmenopausal women and men".)
●Assessment of orthostatic hypotension and tachycardia – Patients suspected of postural orthostatic tachycardia syndrome (POTS) should be assessed clinically with orthostatic pulse and blood pressure testing (increase in pulse of >30 beats per minute (bpm) in changing position from lying supine to standing and/or a fall >20 mmHg in systolic pressure from lying to standing). Patients with abnormal testing should be referred to an expert on these conditions to undergo more detailed assessment. (See "Postural tachycardia syndrome" and "Mechanisms, causes, and evaluation of orthostatic hypotension".)
●Other symptoms and findings – Depending upon the specific clinical findings that may be present, various blood tests and other laboratory studies may by required. As examples, testing for myopathies; endocrinopathies; hematologic disorders, including clotting abnormalities; inflammation; and autoantibodies for autoimmune rheumatic disease may assist in excluding other conditions suggested based upon clinical findings. Thyroid function tests (TFTs) and iron studies should be performed in patients presenting with fatigue. Patients with milder myopathies may present with exercise intolerance and poor recovery, with significant postexercise myalgia that needs specialist assessment.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ehlers-Danlos syndromes and joint hypermobility".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Ehlers-Danlos syndrome (The Basics)")
SUMMARY AND RECOMMENDATIONS
●New definitions and international criteria were adopted in 2017 for hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD), which are characterized by joint hypermobility and other shared clinical features. These terms have supplanted the label joint hypermobility syndrome (JHS), which was previously used for the condition seen in many of these patients (table 1). The precise prevalence of these conditions is unknown; JHS had been estimated to be present in approximately 1 in 500 people in the general population. No structural abnormality in collagen or related proteins or in the genes encoding such molecules has been identified in the vast majority of patients with hEDS. (See 'Terminology' above and 'Epidemiology' above and 'Pathophysiology' above.)
●Joint hypermobility alone is very common in the general population, affecting approximately 10 to 20 percent of individuals to some degree; it may either be present in isolated joints or be more generalized throughout the body. Most people with joint hypermobility alone do not experience any problems from the condition. (See 'Epidemiology' above.)
●The major clinical features in both HSD and hEDS are symptoms and findings related to the musculoskeletal system. In hEDS, there are also skin changes, including fragility of skin and supportive connective tissues, and some features common to other hereditary disorders of connective tissue (HDCT). Additionally, in both HSD and hEDS, systemic features are often present, including chronic widespread pain, fatigue, autonomic dysfunction, and gastrointestinal dysmotility. (See 'Clinical manifestations' above.)
●The diagnosis of HSD and hEDS is made clinically, and that for hEDS based upon the medical history and physical examination, using the 2017 international criteria (table 2), which describe the combinations of musculoskeletal and other historical and clinical findings that may be used to make the diagnosis; there are no diagnostic laboratory tests for HSD or hEDS. A component of the criteria is ascertainment of the Beighton score for joint hypermobility (table 4), which should be evaluated in all patients suspected of having a hypermobility-related disorder. It is important to exclude other conditions with similar or overlapping features, which in some patients may require referral to a medical geneticist or other expert. (See 'Diagnosis' above and 'Beighton score for joint hypermobility' above and 'Features suggesting an alternative diagnosis' above.)
●The differential diagnosis includes the conditions that have generalized joint hypermobility as a clinical feature, particularly Marfan syndrome and other types of Ehlers-Danlos syndrome (EDS). (See 'Differential diagnosis' above.)
●Additional testing may be required to either help establish the diagnosis (eg, by excluding other conditions) or to further characterize symptoms or abnormal findings identified in the history and physical examination; testing depends upon the specific clinical findings and may include imaging of the peripheral joints and spine, laboratory testing to exclude other disorders, echocardiography, bone mineral density testing, evaluation for autonomic dysfunction, and other studies. (See 'Supplemental and postdiagnostic evaluation' above.)
