The main objective of this article is to provide a clinical description of the identification of forms of hypermobility. Secondary objectives are to highlight the best current research available on referral pathways and implications for clinical practice, in order to highlight guidelines for future research. The Ehlers-Danlos Syndrome International Consortium is working to develop evidence-based management and care guidelines.
| Historical perspectives on joint hypermobility |
Joint hypermobility (HA) was recognized as a clinical entity by Hippocrates in the 4th century BC. C., from the observation of it in shot putters or archers. The literature records similar descriptions from contortionists to musicians. Towards the end of the 19th century and the beginning of the 20th century, these descriptions made it possible to gather signs and symptoms with diagnostic characteristics.
In the 1960s, joint hypermobility syndrome (JHS) was defined as “the appearance of symptoms in otherwise healthy hypermobile individuals.” The term Ehlers-Danlos Syndromes (EDS) was ascribed to the field of genetics and dermatology, while the term HA syndrome (HAS) was used in the field of rheumatology .
More recently, specialists in these fields recognized the overlap of these conditions, resulting in agreed-upon terminology attributed to specific diagnoses of Generalized Hypermobility Spectrum Disorder (G-SEH) and Ehlers-Danlos hypermobility syndrome (SHED).
| Current definitions of hypermobility, laxity and instability |
Although used interchangeably, the terms hypermobility, laxity, and joint instability are not synonyms. This is not a new phenomenon. In 1902, reporting on a child with congenital hip dislocation, Ochsner described “hypermobility of the heads of both femurs and of the thighs.” It is likely that he was referring to physiological movement of the hips (hypermobility) and accessory movement of the femoral heads (laxity).
Hypermobility describes the objective measure of a joint moving passively or actively around the axes of motion, beyond normal physiological limits. An example is hyperextension or knee bending . Proposed multidimensional causes of HA include bone morphology/shape seen in humeral and femoral torsion, increased joint surface area, and dysplastic or overly compliant passive restrictions on physiological joint motion.
Laxity describes the objective extent of a joint to passively move beyond normal limits during accessory movement (commonly sliding and twisting) . It is assessed by manual testing such as the Lachman test of the knee, anterior drawer of the ankle, or shoulder, or mechanically (e.g., the KT-3000, a mechanical device that measures tibial displacement for an imposed load). The terms laxity and mechanical instability are often used interchangeably.
Functional instability is a subjective self-report by the patient, described as mistrust or insecurity regarding their joint, even in conditions of low strength. They could describe joint subluxation, slipping out of place, giving way, or downright dislocating. Measurement of functional instability or joint mistrust can be assessed using a questionnaire.
In the absence of functional instability (when dislocation is evident), any signs of hypermobility and laxity may be clinically irrelevant and may even be advantageous . An example would be the gymnast who shows an extreme physiological range of joint motion (hypermobility) and when formally evaluated she shows more extensive accessory movement than could be expected for her age and sex (laxity).
Despite hypermobility and laxity, they do not report that their joints subluxate or dislocate during gymnastic routines or activities of daily living. That is, their joints are not unstable and do not need to be “managed” or medicalized .
When the joints are adequately stabilized by the active system (muscles and tendons), in the presence of adequate proprioception and kinesthesia, such that physiological and accessory movement is controlled, the insufficiency of the passive stabilizers (fascia, ligaments and joint capsules) is concealed. . Affected joints become symptomatic (unstable) when the active system fails , which sometimes occurs after injury or deconditioning.
| Inheritance and acquisition of hypermobility |
The presentation and distribution of HA varies widely among individuals. It can be present in a single joint (monoarticular) or be pauciarticular or oligoarticular (some joints), polyarticular (several joints, often central or peripheral, in upper or lower extremities) or generalized HA, present in all 4 extremities and the skeleton. axial.
These forms of hypermobility can be inherited as a normal trait with no identifiable genetic variant or as part of an inherited syndrome, such as EDS and other inherited connective tissue disorders.
HA can also be acquired through trauma, joint disease, or training.
For example, it has been shown that a baseball player’s shoulder range of motion is greater in the dominant arm than in the non-dominant arm. HA can also occur bilaterally, such as in both knees where the range of extension is greater and increases with training. There are also subpopulations in whom AH appears with activity, such as dancers, musicians, gymnasts and contortionists, in whom a higher prevalence of generalized AH is expected than in the general population.
The underlying determinants of generalized AH remain unknown. Given the characteristic that generalized HA runs in families , it has always been considered an autosomal dominant trait, most likely related to the genes that encode collagen or a collagen-modifying enzyme.
However, the candidate genes involved with generalized AH are closer to AH that sometimes presents as a sign of an inherited connective tissue disorder. For example, one study reported that 5% to 10% of adults with hypermobile EDS show lower serum levels of tenascin-X. This has expanded the field on the candidate genes responsible, since tenascin-X is a large extracellular matrix glycoprotein, the first non-collagenous protein identified with widespread HA under these conditions.
Fragility of connective tissue , the most abundant tissue in the body, may be evident in tendons, septa, fascia, ligaments, and joint capsules, due to deficient structural proteins, such as collagen , elastin, fibrillin, and tenascin . People with inherited connective tissue disorders of genetic causes, such as osteogenesis imperfecta and neuromuscular conditions, commonly have generalized AH.
A broader understanding of the spectrum of generalized HA requires other signs, symptoms, and comorbid conditions. The complex interplay between an individual’s genetic and functional physiological interactions and environmental influences contribute to its phenotypic presentation.
| Traditional and novel assessments of joint hypermobility |
Interest in clinical measurement of HA has grown since the 1960s when Carter and Wilkinson published an assessment tool. This tool was adapted around the world to include other articulations relevant to the specific population.
The Nicholas scale modified this tool for screening soccer players and the Rotes-Querol Scale considered additional tests of shoulder, cervical spine and lumbar spine mobility. Subsequently, the Contompasis score was developed, which included a more complex mobility classification system, incorporating the ankle, while the Hospital del Mar Scale incorporated knee and shoulder rotation. The most used tool today is the Beighton score.
Recent research has shown that degrees of hypermobility vary and therefore recommend variable cut-off points for age, sex, and cohort of interest, based on race, occupation, etc. Recently, more comprehensive peripheral HA tools have been developed to provide greater detail and specific management guidance.
The Upper Limb Hypermobility Assessment Tool (ULHAT) and the Lower Limb Assessment Score3 are 12-item tests that cover the main joints of the upper and lower extremities, in multiple planes of movement. It should be noted that these tools also incorporate some laxity tests (described as passive accessory tests).
There are a few points to consider when using hypermobility assessments. While age- and sex-specific cutoff scores have been determined using the Beighton score, this was not the case for the other tools, nor has any psychometric testing been performed to elucidate the key elements intended to determine limb hypermobility. . Despite a high correlation of mobility between limbs, there are reports that the nondominant limb is more hypermobile than the dominant one and that there are differences between sides due to training effects.
The 5-Part Questionnaire is a valid and reliable self-report questionnaire tool that can be used to measure generalized HA in adults. The tool is particularly useful in adults who have experienced age- and injury-related reduction in joint range.
| Strengths and limitations |
There are tools designed to assess joint range of motion, the reliability of which has already been evaluated. It should be noted that the Beighton score was designed for epidemiological screening and not for clinical use. One of its advantages is that it is quick to perform and, when the joint range is equivocal, it requires only one goniometer. The limitations refer to the large bias in the upper extremities and the incorporation of a limited number of joints since it evaluates movement in a single plane, the sagittal.
Perhaps its most important limitation is that it does not include the joints that patients most frequently describe as unstable, such as the shoulder, foot and ankle, and patellofemoral joints. While the 5-Part Hypermobility Questionnaire has very good sensitivity and specificity for identifying generalized HA, it has only been validated in adults and does not provide information on individual joints.
The more recently developed and validated Lower Limb Assessment Score and the ULHAT have the potential to provide a richer view of joint range and integrity to inform further assessments of function and interventions.
However, these multidimensional assessments require standardized procedures, specialized management, and additional psychometric testing. This knowledge about the strengths and limitations of the assessment should prompt clinicians to apply the most appropriate assessment tool tailored to the signs and symptoms the patient presents.
| Age, sex and racial considerations |
Epidemiological studies report wide variation in the prevalence of hypermobility, depending on the method of clinical assessment, cut-off score used, population, physical fitness, age, sex, and race. The prevalence of HA has been reported to range from 5% to 40% in children and 10% to 20% in adults. Regardless, the prefix “hyper” means that the measure is not “normal ,” where normal represents the mean and scores within 2 SDs for a population, taking into account age, sex, and race.
There is significant complexity in assessing range of motion in infants and children. Infant joint range of motion depends on the gestational age of the newborn and is difficult to assess accurately due to lack of bony reference points and difficulty determining precise planes of motion.
After the first few years, children usually have greater joint mobility than adults. Current assessments of generalized AH have not been validated in children <5 years of age and, as such, cannot be used to accurately identify generalized AH in this age range. If age, gender, and race-specific norms are available for individual joints, they can only be used to determine hypermobility in individual joints in children.
Children who exhibit greater mobility in multiple individual joints, then these can be identified simultaneously. In children with suspected generalized HA and any potentially associated symptoms or concerns present during the pediatric years, continuous joint range monitoring is recommended before labeling with genetically unconfirmed conditions related to generalized HA.
Although it is well described that the prevalence of generalized HA decreases with age, it is not clear which children will continue to show generalized HA and which will “get stronger” after puberty.”
AH is more common in women than in men.
Although similar age-related trends in AH have been reported in both sexes, the decline in joint mobility after puberty is usually more pronounced in men. Proposed explanations for these sex-related differences include, but are not limited to, hormonal, anatomical, and neuromuscular differences.
Regarding the racial variation of HA, several studies suggest a higher prevalence in people of African, Asian and Middle Eastern descent, compared to white populations. It is unfortunate that most HA studies do not report the race of the participants. Most of those who do so mention a higher prevalence in the white race. Consequently, it is not possible to do subanalyses to determine the effect of breed on AH and related signs and symptoms.
| Phenotypic presentations of joint hypermobility |
Most people with HA remain asymptomatic throughout their lives. If present in otherwise healthy individuals, without associated symptoms or complications, this hypermobility is called “asymptomatic joint hypermobility.”
When hypermobility is polyarticular or generalized, these individuals often describe themselves as "double jointed" and may undertake activities for which HA is an advantage, such as dancing, music, gymnastics, and contortion.
The symptomatic threshold can be reached when there are multiple risk factors for the onset of pain in or near a hypermobile joint. These factors include muscle weakness, reduced mobility, insufficient musculotendinous length, muscle hypertonicity in proximity to a hypermobile joint, obesity, and altered movement patterns. If AH is present in combination with pain, recurrent (sub)luxations, and musculoskeletal overuse injury disorders, it can be categorized as “symptomatic joint hypermobility.”
Decreased functional capacity, lower isometric strength, suboptimal muscle activation strategy, and quality of force control have been reported in people with symptoms of joint AH. Despite increasing attention over the past decade, researchers and clinicians are still exploring the determinants that cause AH to become symptomatic.
The symptoms of hypermobile patients can extend far beyond the limits of the musculoskeletal system.
Approximately two-thirds of patients with symptomatic AH also report several multisystem functional symptoms, including, but not limited to, gastrointestinal dysfunction, orthostatic intolerance, postural orthostatic tachycardia syndrome, urogynecological problems, mast cell activation symptoms, physical and cognitive fatigue, and anxiety and depression , constituting a syndromic presentation.
Currently, there is an association between generalized AH and many of these conditions, but it remains unknown whether the same underlying pathology drives some or all of the reported multisystem features, or whether they are the result of other associated factors, such as lack of condition. physical or chronic widespread pain and chronic fatigue, which are nonspecific symptoms.
Some proposed pathogenesis relate AH to other multisystem conditions. For example, orthostatic intolerance may be attributed to increased vascular compliance resulting from altered connective tissue or peripheral small fiber neuropathy, while gastrointestinal disorders are related to autonomic dysfunction/dysmotility, interoceptive sensitivity, and/or impaired stretching and mechanoreceptor function of the intestines. The pathogenesis of an association between mast cell activation and HA has not yet been determined.
The mechanisms behind the complex pain states that can be observed in this latter subgroup of hypermobile individuals are poorly understood. Posterior capsuloligamentous and other soft tissue injuries along with peripheral nerve irritation due to compression, elongation, or entrapment are some of the proposed mechanisms. The symptom profile can vary widely between patients, with a wide spectrum of severity.
If a hypermobile patient also presents with multiple orthopedic and skin abnormalities and vascular fragility, and reports multiple signs of tissue fragility, screening for an underlying hereditary condition is warranted, to ensure appropriate medical care and follow-up, and to avoid more serious complications. Examples of such pathologies are hereditary connective tissue disorders such as Marfan syndrome, EDS, osteogenesis imperfecta, and Stickler syndrome. Other chromosomal disorders, such as Down syndrome, and metabolic disorders such as homocystinuria and hyperlysinemia may also be part of the differential diagnoses.
The characteristics that alert the doctor to attribute the signs and symptoms to a hereditary syndrome are :
1. Tissue fragility, bone fragility (recurrent fractures) and/or tissue fragility (abdominal hernia or prolapse of the bladder, uterus or intestine) or organ fragility (rupture of hollow organs). The most important thing to recognize is vascular fragility (easy bruising, tendency to bleed, vascular aneurysms, dilations or dissections) associated with Marfan syndrome, vascular EDS, familial thoracic aortic aneurysm, etc.
2. Skin fragility and altered skin structure, soft skin with a velvety surface, elastic skin, hyperextensible skin, atrophic scarring, presence of multiple scars, delayed wound healing, wound dehiscence, etc.
3. Orthopedic deformities: pectoral deformity, congenital clubfoot, short or tall stature, congenital scoliosis, hip dysplasia and/or congenital bilateral hip dislocations, increased arm span in relation to length, arachnodactyly, etc.
| Generalized hypermobility spectrum disorders and hypermobile Ehlers-Danlos syndrome |
The authors state that consistent diagnostic terminology and standardized, validated assessments are important facilitators for research, evidence-based treatments, and communication between healthcare providers and patients. Thus, they have presented the terminology of hypermobility, the different signs and symptoms of generalized AH and how to evaluate them. This exploration allowed them to arrive at diagnostic labels that are currently adopted. Previous diagnoses of HA syndrome or hypermobility types of EDS, considered essentially the same condition, were reviewed in 2017.
It emerged from this review that for people with HA not otherwise classified, the term hypermobile EDS should be restricted to those with features suggestive of a systemic and/or Mendelian connective tissue disorder.
According to a study of population-based healthcare records in Wales, the prevalence of HA syndrome is likely to correspond to a combination of what is currently diagnosed as hypermobile EDS and generalized hypermobility spectrum disorder. This prevalence was calculated at 1/500-600. Of the 13 types of EDS, hypermobile is the most common and represents more than 95% of all reasons for consultation in specialized clinics.
The conditions generalized HA syndrome and hypermobile EDS share many clinical features, including generalized HA, joint instability, and chronic generalized pain, all of which are included in the criteria for both diagnoses. The new diagnostic labels of hypermobile EDS and generalized HA syndrome have caused some confusion among researchers, clinicians, and patients, and from a symptom management perspective, the 2 conditions can be managed identically.
Management of presentations of heterogeneous multisystem signs and symptoms must be personalized. More pertinent to management is that thorough history taking and clinical evaluation must be combined with equally thorough clinical reasoning, informed by the patient’s expectations and goals.
Currently, the diagnostic criteria for hypermobile EDS are not valid for use in children and adolescents as they have multiple multisystem features that comprise criterion 2 of the 2017 classification, and are not appropriate for childhood evaluation. For example, atrophic scarring cannot be seen in a young child who has not had a skin tear while dental crowding cannot be determined in a child whose permanent teeth have not yet erupted.
In light of these difficulties, to apply the current criteria in children, the development of specific pediatric criteria is expected, such as the one being carried out by the Pediatric Working Group of the International Consortium on EDS and AH Spectrum Disorders. Until that time, children should be monitored to document changes in generalized AH and other potentially associated multisystem features, until skeletal maturity is reached, at which time the diagnosis is labeled as hypermobile EDS, and can be reassessed using diagnostic criteria to Adults.
| Clinical implications and research guidelines |
The heterogeneity of measurement outcomes reported in the literature has hampered attempts to produce clinical evaluation and management guidelines. The EDS Society is currently collecting self-report and objective outcome measures, including those appropriate for the assessment of hypermobility, and standardizing their use in this population globally.
Commonly, AH is more asymptomatic, and only surveillance, risk identification and management, prevention of task-specific injuries, or performance improvement are warranted. This form of hypermobility does not need to be medicalized.
In these cases, the Beighton score works well for screening. However, in those who experience symptoms associated with their HA, a more extensive evaluation is necessary to determine the joint(s) and plane(s) of motion affected along with objective and patient-specific functional evaluations, which will allow for their best performance. driving. For example, a patient who describes shoulder instability and shows 3 positive ULHAT shoulder tests and demonstrates functional movement deficiencies may be better managed with exercises that improve strength and control in more than one anatomical plane.
Although it is important to focus on a diagnosis, from a clinical/management standpoint, the focus should be on each patient’s presentation of symptoms.
Patients diagnosed with generalized AH spectrum disorder may be poorly managed due to the perception that their condition is less severe than hypermobile EDS. Finally, future research is warranted to validate the diagnostic criteria. The, self-reports and physical measurements in the pediatric population.
| Conclusions |
Joint hypermobility presents on a spectrum ranging from an asymptomatic physiological phenomenon to a component of a complex myriad of multisystem presentations.
