Hypermobility syndrome was recognized as a distinct pathology by Kirk et al1 in 1967. Since then, the syndrome has been identified by a variety of names: “hypermobility syndrome (HMS),”2–9 “joint hypermobility syndrome,”10–13 “hypermobile joint syndrome,”14 and “benign hypermobile joint syndrome.”15,16 Other reports do not recognize this disorder as a syndrome, but refer to the manifestations of joint hyperlaxity, joint hypermobility, or articular hypermobility. In the International Nosology of Heritable Disorders of Connective Tissue, Beighton et al17 identified this syndrome as “familial articular hypermobility syndrome.” Beighton et al excluded genetic diseases that include joint hypermobility as an associated finding, such as Ehlers-Danlos syndrome, osteogenesis imperfecta, and Marfan syndrome.
Despite the proliferation of names, HMS has been given relatively little attention in the literature. Most reports are in the rheumatology literature, with virtually none in the orthopedic or physical therapy literature. This lack of reports may be due to several reasons. First, individuals with HMS are often seen by orthopedic physicians and physical therapists as a result of an acute or chronic disorder, which may be treated without the health care provider acknowledging the underlying HMS. Second, the diagnostic criteria for HMS are not well-defined and have not been consistent among research reports.8,18–20 In particular, patients with HMS lack laboratory or radiological findings that could identify HMS, unlike many other rheumatologic or orthopedic conditions. The diagnosis, therefore, is frequently made through exclusion of other disorders. Third, individuals with HMS often do not have the decreased mobility seen with many chronic conditions,4 nor do they always have the inflammation seen with many acute conditions. Finally, because HMS lacks a definitive pharmacological or surgical treatment, physicians may have perceived little benefit in its diagnosis.
Patients with HMS often have complaints that are frequently diffuse, chronic, and inconsistent with observed pathology. These individuals may be improperly identified as having hypochondria, as malingering, or as having nonspecific chronic pain, without further investigation into the source of their complaints.11,21 Individuals with HMS may not get a diagnosis, or they might be misdiagnosed.22 Failure to recognize the underlying HMS may lead to unnecessary or inappropriate diagnostic studies, surgical procedures, and patient management,23 especially for children.24
Some reports of HMS describe it as “benign” when compared with the serious connective tissue diseases that have hypermobility as one of their signs.15,16,25,26 Hypermobility syndrome has also been described as representing the upper end of the normal distribution for ligamentous laxity,27,28 with no greater incidence of pain or injury.29,30 Some authors25,31–34 have even proposed that hypermobility may be an asset in certain sports or professions. The mobility present in people with HMS, however, is considered beyond the normal range by most researchers,6 with repeated reports describing increased incidence of pain and associated disorders (Tab. 1).
A goal of this update is to increase awareness, understanding, and discussion of HMS through examination of the prevalence, diagnosis, clinical presentation, and pathophysiology. Although physical therapy for people with HMS has been recommended by many authors,2,3,11,26,35 there are no published reports regarding the efficacy of physical therapy or any other treatment for individuals with HMS. Hopefully, increased recognition will lead to increased research about this disorder.
Reports of the prevalence of HMS must be viewed cautiously because of the variability in the diagnostic criteria used. Hypermobility syndrome has been reported in 0.6%18 to 31.5%36 of adults without joint pain, depending on age, ethnicity, and criteria for assessing hypermobility (Tab. 2).37 This syndrome is more prevalent among females than among males.15,18,36–41 Reports indicate that HMS may be from 1.1 times42 to 5.5 times18 more prevalent among females than among males. Hypermobility syndrome is also more prevalent among Asians than among Africans, and it is more prevalent among Africans than among Caucasians.4,39 Children without symptoms of HMS tend to have rates of hypermobility that are higher than those of adults (between 6.7%19 and 39.6%42), again depending on the population and criteria used (Tab. 2). Hypermobility appears to decrease with age.18,43–45
In children with fibromyalgia, the prevalence of hypermobility may be as high as 81.0% (Tab. 3).21 Not all groups with joint pain described in Table 3, however, had high rates of HMS. For example, only 2.9% of children with juvenile rheumatoid arthritis (RA) had HMS versus 65.6% of those with juvenile episodic arthritis or arthralgia.38 In a study of adults,46 32.0% of patients without hypermobility who were seen in a rheumatology clinic had inflammatory arthritis, compared to only 4.3% of patients with hypermobility.
Carter and Wilkinson19 proposed the first scale for rating hypermobility syndrome, in which one point was given if the patient could do each of the following indicators of HMS: passive apposition of the thumb to the forearm, passive hyperextension of the fingers and wrist so that the fingers lie parallel to the forearm, hyperextension of the elbow past 10 degrees, hyperextension of the knee past 10 degrees, and excessive dorsiflexion and eversion of the foot. They proposed that a score of 3/5 or higher indicated HMS.
Beighton et al18 modified these criteria, providing the diagnostic criteria most commonly used today and still considered the yardstick for proposed scales.4 The Beighton scale gives a patient one point for each of the following characteristics: passive extension of the fifth metacarpophalangeal (MCP) joint past 90 degrees, passive apposition of the thumb to the forearm, hyperextension of the elbow past 10 degrees, hyperextension of the knee past 10 degrees, and trunk flexion allowing the palms to be placed flat on the floor. Beighton et al scored each limb separately for the first 4 items, generating a possible score of 9. Subsequent researchers have sometimes combined right and left sides, generating a possible score of 5. There is no universal agreement on a threshold for HMS; some researchers use a Beighton scale score of 5/9, other researchers use a Beighton scale score of 6/9, and still other researchers use a modified Beighton score of 3/5 (Tab. 2).
Bulbena et al8 compared the hypermobility scale proposed by Carter and Wilkinson,19 the modified scale of Beighton et al,18 and an 11-point scale proposed by Roté.20 Along with other criteria, Bulbena et al determined which criteria most clearly distinguished individuals with HMS from a control group of patients without HMS who were seen in a rheumatology clinic. Bulbena et al found each of the scores to be highly correlated to the other scores. By doing a cluster analysis, they were able to identify the 10 criteria most highly predictive of HMS. The frequency of positive criteria seen in patients identified as having HMS is shown in Table 4. Several, but not all, of the common findings are included in Carter and Wilkinson's criteria and in Beighton and colleagues' criteria. Bulbena et al also proposed that there be different cutoff criteria for women and men, as women tend to have more positive signs than men have. This discussion shows that there are neither agreed on criteria nor agreed on scores for the diagnosis of HMS.
Attempts to more precisely quantify hypermobility have been proposed, including controlled hyperextension of the fifth finger using a hyperextensometer47 (a mechanical device that hyperextends the MCP joint using a controlled torque) and other measuring devices that use a controlled torque to apply passive overpressure.28
Global measures, however, appear to have greater sensitivity for identifying people with HMS than do isolated hyperextensometric measures.33 Symptoms do not appear to be directly correlated to the number of joints involved.23 That is, individuals with marginal scores on these tests may have more symptoms than do individuals with high scores.
Laboratory tests may be done to rule out related but more serious disorders (eg, RA and other inflammatory polyarthritic conditions,1 Ehler-Danlon and Marfan syndromes). The increased collagenase and protease breakdown of articular cartilage that is seen in people with RA is not seen in people with HMS. If the patient has Ehlers-Danlos or Marfan syndrome, both of which are hereditary connective tissue disorders with associated joint hypermobility,39,48 the diagnosis of HMS is precluded.8,26,49 Findings of hyperelastic skin, hernias, lenticular abnormalities,6 and abnormal body proportions1 are seen in patients with Ehlers-Danlos or Marfan syndrome but not in patients with HMS. Easy bruising and poor wound healing may be seen in patients with HMS as well as in patients with Ehlers-Danlos or Marfan syndrome. Osteogenesis imperfecta is another collagen disorder that may need to be ruled out, even though patients with this disorder often demonstrate joint hypermobility.50 Systemic lupus erythematosus,51 poliomyelitis, tabes dorsalis, myotonia congenita, and some neurological conditions1 are also excluded.
People with HMS may have complaints that have lasted from 15 days to 45 years (average time=6.5 years), and the onset of symptoms may occur at any age from 3 to 70 years.6 These individuals may go to an orthopedic physician, rheumatologist, pediatrician, or physical therapist with any of a wide range of traumatic or nontraumatic pain complaints (Tab. 1). Frequently, these individuals report multiple complaints over a prolonged period. They typically lack the positive laboratory findings found in rheumatologic disorders and, in the absence of acute trauma, lack the radiologic changes, inflammation, swelling, and decreased mobility typical of orthopedic pathology. Patients with HMS often have a poor response to oral analgesic and anti-inflammatory medications, unless they have inflammation due to recent trauma.11
People with HMS may have an increased incidence of nerve compression disorders, although data are scant. El-Shahaly and el-Sherif6 reported acroparesthesia (excessive paresthesia in multiple limbs) in 57.9% of the 114 patients with HMS they tested. They found carpal tunnel syndrome in 31.6% of the patients and tarsal tunnel syndrome in 14.0% of the patients. They also reported a greater incidence of paresthesia among women than among men. Hudson et al,8,46 however, reported no difference in nerve entrapment neuropathies between patients with HMS and a control group referred to a rheumatology clinic (data were not presented). In that study, which included patients with thoracic outlet syndrome and musculoskeletal complaints, the authors found that 54.3% of the patients with HMS had thoracic outlet symptoms (they did not compare patients with HMS and patients without HMS in their study).
Patients may also have sequellae of HMS.49,52 Some authors6,51 reported that up to 60% of individuals with HMS developed osteoarthritis (OA) as opposed to 30% of patients without HMS who were seen in a rheumatology clinic. Other researchers53 found that 24% of patients with OA had HMS, as opposed to only 8% of patients seen for general medical conditions. An increased incidence of OA may be secondary to chronic or traumatic biomechanical abnormalities or proprioceptive deficits. Mobile joints such as the patellofemoral joint and the mid-cervical spine seem to be affected most.54,55 Hypermobility syndrome was more common in patients with chondromalacia patellae than in matched controls.56 Articular cartilage is made up of primarily type II cartilage, and it is suspected that HMS may include an abnormality of type II collagen.54
Although sprains, subluxations, and dislocations are more common in people with HMS,3,57–59 the amount of tissue damage occurring with these acute injuries may actually be decreased due to the increased laxity of joint structures. For example, patients with HMS and acute patellar dislocation had an incidence of chondral injury and avulsion fracture of only 33%, whereas patients without hypermobility had an 80% incidence.59
Many researchers60–62 have found a correlation between temporomandibular dysfunction (TMD) and HMS, with up to 54.3% of patients with TMD demonstrating HMS. One study14 also showed that individuals with HMS had abnormal disk position and excessive anterior mandibular movement. Not all researchers found this association between generalized hypermobility and TMD.63
Infants with HMS have higher incidences of motor delay, even in the absence of an identified neurological deficit. Among infants between 8 and 14 months of age, 30.2% of those with HMS had motor delay versus 10.9% of infants without HMS. Six months later, 75.9% of the infants with HMS no longer had hypermobility; 83.3% of these infants caught up in motor development, whereas only 54.5% of the infants who remained hypermobile caught up.43 At 5 years of age, children who had hypermobility and motor delay at age 18 months were 3 times as likely as other children to have motor delay.44 Other reports have shown no motor delay in elementary school children with HMS.64
People with HMS are more likely (69.3%) to have anxiety disorders than are comparison groups with rheumatological conditions (22.0%)10 or groups with other chronic medical conditions (21.3%).65 The incidence of anxiety disorders among individuals with HMS was 3 times greater when mitral valve prolapse (a common finding with HMS) was present.10 Anxiety may also be due to the perception of joint instability and frequent pain and injury without understandable antecedent.
The high incidence of psychological disorders in people with HMS is similar to that seen with fibromyalgia.66,67 Ninety percent of individuals with HMS and fibromyalgia reported sleep disturbances.68 Because HMS and fibromyalgia appear to be related, the causes of psychological disorders in people with HMS may be similar to those proposed for fibromyalgia: abnormalities in serotonin metabolism, stage IV sleep patterns, and levels of substance P,22,69 or perceptual hypervigilance.70
Other systemic findings are highly correlated with HMS. Mitral valve prolapse is 3 times more prevalent in patients with HMS than in other patients and may be present in up to one third of all individuals with HMS.5,10,12,51,71 Uterine prolapse is also more common,6,72,73 as are rectal prolapse74 and abdominal hernias.75 An increased incidence of varicose veins has been reported by some authors6 as has increased bruising.10,71 Increased skin elasticity and decreased skin thickness in patients with HMS has been documented by some authors16 but not by others.71 One surgeon reported wide, thin scar formation after surgery in patients with HMS.58
Some authors12 have reported morphological differences in subjects with HMS: arm span greater than height, wide-set eyes, beaked nose, slim fingers. Studies, however, that specifically exclude individuals with Marfan or Ehlers-Danlos syndrome (as specified in the diagnosis17,26) typically do not show morphological differences.
Hypermobility syndrome appears to be inherited as a gender-influenced dominant trait.11,13,17,19,34,76 It appears to be an abnormality of type I collagen,11 although studies to identify a single gene abnormality have not been successful.15 Other collagen diseases have also been related to multiple collagen or genetic abnormalities.77
Type I collagen is the most common collagen in the human body. With a high tensile strength, type I collagen is normally abundant in connective tissues such as tendon, ligament, joint capsule, skin, demineralized bone, and nerve receptors. Type II collagen is found primarily in hyaline cartilage. Type III collagen is found in the same tissues as type I collagen, but usually in lesser amounts. Thin and elastic compared with type I collagen, type III collagen is found in greater relative amounts in extensible connective tissues, such as the vascular system, skin, and lung.78 In patients with HMS, the ratio of type III collagen to type III+type I collagen is increased.11,12 Normally, this ratio is 18%:21%, whereas in patients with HMS, it is 28%:46%. Electron microscopy of skin biopsies showed that individuals with HMS had a decreased number of thick collagen fibers and an increased prevalence of fine disorganized fibers when compared with age-matched controls.12 The abnormal ratio of type III to type I collagen is thought to cause the decreased tissue stiffness seen in patients with HMS. Decreased stiffness of joint structures produces the joint hypermobility most obvious in patients with HMS; decreased stiffness of other tissues may result in the prolapse seen in other organs. For example, aortic compliance is increased in patients with HMS.12 Mitral valve prolapse is thus caused by decreased stiffness of the chordae tendineae that normally limit valve movement.
Nerve tissue also appears to be affected in patients with HMS. The increased incidence of acroparesthesia reported in individuals with HMS6 may be due to abnormalities in the nerve tissue as well as surrounding connective tissues. Individuals with HMS are less accurate than individuals without HMS in reproducing a proximal interphalangeal joint angle.7 Studies have shown that position sense at the knee is also decreased in patients with HMS. In particular, subjects with HMS did not have the ability to locate their joint at end-range extension found in subjects without symptoms of HMS.9 Increased mobility and decreased joint position sense could make the joints of people with HMS more vulnerable to damage from what would be minor trauma in a person without symptoms of HMS.
Treatment of Patients With Hypermobility Syndrome
Education is probably the most important treatment that physical therapists can provide to individuals with HMS. Because people with spinal hypermobility are reported to have a higher incidence of back pain in sedentary jobs,32 it seems likely that education regarding ergonomics and body mechanics may decrease the incidence of back pain among people with HMS. As education about joint protection has been shown to increase function and decrease pain in subjects with RA, education regarding joint protection in HMS may similarly decrease pain, traumatic injury, and subsequent degenerative disease in vulnerable joints.79 It seems appropriate to advise individuals with HMS in the selection of jobs, sports, or recreational activities that will not exacerbate their condition. In theory, patients with HMS may be able to continue certain activities at a decreased frequency or intensity or be able to modify biomechanical stresses through change in technique or use of protective splints for vulnerable joints. Splints, braces, and taping may also be used judiciously to protect other vulnerable joints.2
Helping patients with HMS understand their disorder may help them cope with the pain they experience. Goldman68 found that for individuals with both fibromyalgia and HMS, the presence of HMS was associated with increased participation in a treatment regimen. He attributed increased participation to the improved understanding and acceptance patients had for their disorder.
Although exercise will not increase stiffness of the lax ligaments seen in patients with HMS, strengthening and proprioceptive exercises are recommended for musculature surrounding affected joints.2,3,9,35,80–83 Individuals with HMS and fibromyalgia who exercised reported greater improvement in symptoms than did those who did not exercise.68 Indiscriminant exercise, however, could be harmful. For example, lightweight women rowers who had excessive spinal mobility were more likely to have back problems if they participated in a stretching program for their backs.84 It appears reasonable, therefore, to advise individuals with HMS to use stretching exercises cautiously, distinguishing between stretching muscles and stretching joints, as the former may be beneficial but the latter may be harmful.
Directions for Future Research
Many unanswered questions remain regarding HMS. Prospective studies of physical therapist patients are needed to determine the percentage of patients with HMS. Such studies could determine, for example, how many patients with HMS have musculoskeletal problems versus nerve compression disorders.
Although many authors recommend exercise for these patients, few have any data on which to base that recommendation. Moderate- and low-impact strengthening exercises, cardiovascular exercise for weight control, and stretching of muscles rather than joints seem theoretically sound recommendations, but the assumptions on which these recommendations are based must be tested. Given the predisposition of patients with HMS for cumulative trauma injuries, studies are needed to determine how much exercise is appropriate for these individuals. The use of orthotic devices, braces, and taping for patients with HMS also warrants further research.
This work was partially supported by Physiotherapy Associates, Memphis, Tenn, and by Department of Physical Therapy, Clarkson University.
- Physical Therapy