joint hypermobility syndrome

7/15/2014 Joint hypermobility syndrome

http://www.uptodate.com/contents/joint-hypermobility-syndrome?topicKey=RHEUM%2F5591&elapsedTimeMs=3&source=machineLearning&searchTerm 1/21

Official reprint from UpToDate www.uptodate.com 2014 UpToDate

AuthorsRodney Grahame, MDAlan J Hakim, BA MB BChir

Section EditorPeter H Schur, MD

Deputy EditorPaul L Romain, MD

Joint hypermobility syndrome

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jun 2014. | This topic last updated: Jul 10, 2014.

INTRODUCTION The joint hypermobility syndrome (JHS) is the most common disorder among the hereditary

disorders of connective tissue (HDCT), a group of conditions that include JHS, the Ehlers-Danlos syndromes

(EDS), Marfan syndrome, osteogenesis imperfecta, and Stickler syndrome. Joint hypermobility (JHM) may be of

no medical consequence and might even confer advantages for dancers, musicians, and athletes; however, it

may also be associated with a number of comorbidities that constitute the cardinal features of the HDCT.

JHS is considered by many experts to be indistinguishable from, if not identical to, the most common variant of

Ehlers-Danlos syndrome (EDS), EDS-hypermobility type (EDS-HM). (See 'Epidemiology' below.)

JHS is reviewed here. Overviews of the clinical manifestations, diagnosis, and management of the Ehlers-Danlos

syndromes; the clinical manifestations and treatment of the Marfan syndrome; osteogenesis imperfecta; and the

Stickler syndrome are 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: Clinical features and

diagnosis" and "Osteogenesis imperfecta: Management and prognosis" and "Syndromes with craniofacial

abnormalities", section on 'Stickler and Marshall syndromes'.)

EPIDEMIOLOGY Joint hypermobility syndrome (JHS) is very common in musculoskeletal disease clinics,

but the diagnosis is often missed, and the actual prevalence of JHS is not known [1,2]. In one large survey in

the UK, the combination of joint hypermobility (JHM) and chronic widespread pain, which is typical of many

patients with JHS, was found in 3 percent of a general population [3]. There has been a lack of general

population studies or other studies of sufficient sample size to accurately estimate the prevalence of JHS [4].

JHS is considered by many experts in rheumatology and in clinical genetics to be indistinguishable from, if not

identical to, the most common variant of Ehlers-Danlos syndrome (EDS), EDS-hypermobility type (EDS-HM),

but the precise relationship between EDS-HM and JHS remains uncertain [5]. (See "Clinical manifestations and

diagnosis of Ehlers-Danlos syndromes".)

JHM alone is very 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. It is more

common in childhood and adolescence, in females, and in Asians and West Africans. JHM tends to lessen with

aging, and has strong heritability [6].

NATURAL HISTORY Untreated individuals with joint hypermobility syndrome (JHS) may develop recurrent

soft tissue injuries, fatigue, chronic regional or widespread pain, declining physical condition, anxiety states,

and autonomic cardiovascular and bowel disturbance, but the frequency of each of these problems among

patients with JHS is uncertain. When present, these conditions can have a major impact on activities of daily

living and quality of life if not remedied [7-10].

PATHOPHYSIOLOGY The pathophysiologic basis of joint hypermobility syndrome (JHS) and Ehlers-Danlos

syndrome-hypermobility type (EDS-HM) is not fully understood. 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 JHS

[11]; an exception is a small population with the JHS or EDS-HM phenotype (less than 10 percent of patients

with JHS or EDS-HM) in whom a deficiency of tenascin X, a large extracellular matrix glycoprotein, has been



described due to alterations in the TNXB gene or haploinsufficiency of the gene [12,13]. The pattern of

occurrence of JHS or EDS-HM in families is generally consistent with a dominant inheritance, but the

penetrance of signs and symptoms is highly variable among family members.

The lack of a well-defined biologic marker in JHS contrasts with other hereditary disorders of connective tissue

(HDCT), including other forms of EDS and Marfan syndrome, for which abnormalities in collagen and fibrillin

biology and associated genetic polymorphisms are well documented.

Abnormalities that appear either unrelated or only indirectly related to connective tissue abnormalities have also

been identified in JHS and may contribute to the pathogenesis of the clinical syndrome. These include the

following:

CLINICAL MANIFESTATIONS The major clinical features of the joint hypermobility syndrome (JHS) include

symptoms and findings related to the musculoskeletal and skin changes, including joint hypermobility (JHM)

(picture 1A-D), 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. Additionally, systemic features, including chronic widespread pain, fatigue,

autonomic dysfunction, and gastrointestinal dysmotility, are often present in patients with JHS, which exhibits a

complex spectrum of signs of symptoms of varying degrees and combinations [4,24]. Estimates of the

prevalence of various manifestations of JHS are generally based upon studies performed with the population

seen in specialist clinical centers and our experience in such settings; the severity of disease and the

prevalence of specific disease manifestations is likely to be less in the general population, but accurate

community-based estimates are not available [4,24].

Patients may present with any combination of the following:

Poor proprioception is associated with joint hypermobility (JHM) [14].

Pain 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].

Fatigue related to the JHS is most likely a manifestation of chronic pain and poor sleep due to pain, and

may also occur as a symptom of autonomic dysfunction [16].

There is a strong association of JHS with cardiovascular autonomic dysfunction [17,18], bowel anatomical

and autonomic dysfunction [19,20], and bladder dysfunction [21].

Anxiety states, which are overrepresented in JHS patients, may have a genetic linkage in about 15 percent

of such patients [22]. The observed prevalence of anxiety is higher than other pain states, but the basis for

this is not fully understood [23]. One factor may be the concerns of patients regarding the multiple

comorbidities associated with JHM for which the relationship with JHS is often not appreciated.

Musculoskeletal manifestations, which are present in patients with JHS, and may include:

Recurrent acute pain from joint sprains and ligament and tendon injuries (universally present in JHS)

Recurrent joint subluxations (incomplete dislocation) or dislocations (common in JHS)

Injuries due to poor proprioception, which leads to clumsiness and loss of balance (present in most

patients with JHS)

Features of the Marfanoid body habitus (a range of skeletal disproportions associated with increased

length and decreased breadth of long bones) (table 1), which are common in JHS, being seen in 60

percent of adult males and 31 percent of adult females with JHS, based upon the authors

unpublished data

Skin manifestations, which are usually mild but are present in all patients with JHS, and may include:

Hyperextensible skin (picture 2), the texture of which is usually soft and silky; the skin is often

perceptibly thin and may be semitransparent, with veins and tendons on dorsum of hand appearing

as if viewed through frosted glass



DIAGNOSIS The diagnosis of joint hypermobility syndrome (JHS) is made clinically, based upon the medical

history and physical examination, using the Brighton 1998 criteria for JHS (table 2), which describes the

combinations of musculoskeletal and other historical and clinical findings that may be used to make the

diagnosis [25]; there are no diagnostic laboratory tests (eg, blood tests, molecular genetic analyses, imaging,

or pathology) for JHS.

Patients with clinical manifestations suggestive of JHS (see 'Clinical manifestations' above) should undergo a

diagnostic evaluation, including ascertainment of their degree of joint hypermobility using the Beighton

hypermobility score (table 3), one of the components of the Brighton criteria, and assessment for historical

evidence of joint hypermobility (JHM) (see 'Beighton score for joint hypermobility' below).

Not every person with widespread pain and hypermobility has JHS; however, many such patients do have JHS,

and patients presenting with widespread musculoskeletal pain may benefit from being evaluated clinically for the

possibility of JHS.

Beighton score for joint hypermobility JHM should be evaluated in all patients suspected of JHS. JHM is

ascertained by determination of their Beighton score, which depends on the presence of JHM in the hands,

elbows, lumbar spine, and knees using specific examination techniques (table 3). One point is awarded for the

ability to perform each of nine maneuvers (including four maneuvers tested bilaterally and evaluation of the

spine). A score of 4 or more points represents generalized hypermobility. The specific maneuvers include:

The presence of JHM can be documented by an examination limited to those areas required for calculating the

Beighton score, but an examination for JHM 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 the

Easy bruising

Wide, paper-thin, and often sunken scars

Multiple stretch marks (striae atrophicae), typically arising during the adolescent growth spurt

Gastrointestinal and genito-urinary (including gynecologic) manifestations of connective tissue laxity (50

percent of patients):

Hernias, including hiatus hernia with gastro-esophageal reflux

Bowel symptoms suggestive of irritable bowel syndrome (constipation alternating with diarrhea,

bloating, nausea and pain) and early satiety

Pelvic floor weakness with bladder dysfunction (dysuria, urgency, frequency, urge and stress incontinence)

Chronic pain (approximately 60 percent), cardiovascular autonomic dysfunction (approximately 30

percent), and other symptoms:

Sustained chronic widespread and localized pain due both to injuries and neuropathic pain (most

patients)

Chronic fatigue (approximately 90 percent)

Anxiety, depression, and phobia (eg, kinesophobia, fear of movement) (15 to 30 percent)

Palpitations, chest pain, and near-syncope or syncope due to postural tachycardia (30 percent)

Orthostatic symptoms, including (near) blackouts due to postural hypotension (30 percent)

Varicose veins, which are uncommon

Eye abnormalities, such as drooping eyelids, myopia, and a downward slant of the palpebral fissure

by which the lateral canthus is lower than the medial canthus

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



temporomandibular joints, shoulders, hips, cervical and thoracic spine, ankles, and feet.

In addition to determination of the Beighton score based upon the examination, the presence of generalized

JHM, including its presence historically, may also be suspected in patients who answer yes to two or more

questions in a simple five-part questionnaire (table 4) [26]:

Brighton criteria for JHS diagnosis The diagnosis of JHS can be made based upon the Brighton 1998

criteria (table 2) [25]. JHS is diagnosed in the presence of the two major criteria, one major and two minor

criteria, or four minor criteria. Two minor criteria suffice where there is an unequivocally affected first-degree

relative. JHS is excluded by the presence of Marfan or Ehlers-Danlos syndromes (EDS), other than EDS

hypermobility type (formerly EDS III) as classified respectively in the Ghent [27] and Villefranche [28] criteria.

DIFFERENTIAL DIAGNOSIS The differential diagnosis for joint hypermobility syndrome (JHS) includes the

conditions that have generalized joint hypermobility (JHM) as a clinical feature, particularly Marfan syndrome

and Ehlers-Danlos syndromes (EDS), other than EDS-hypermobility type (EDS-HM, formerly termed EDS III).

Marfan syndrome is the principal diagnosis to exclude, although there are a number of conditions that may be

associated with JHM [24].

Marfan syndrome JHM is common to the JHS and Marfan syndrome, and the Marfanoid habitus (table 1) ,

which is characteristic of Marfan syndrome, is common in patients with JHS. 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,

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?

Major criteria:

A Beighton score of 4/9 or greater (currently or historically) (see 'Beighton score for joint

hypermobility' above)

Arthralgia for longer than three months in four or more joints

Minor criteria:

A Beighton score of 1, 2, or 3/9 (or 0 if at least 50 years of age) (the major and minor criteria using

the Beighton score are mutually exclusive).

At least three months of arthralgia in one to three joints or back pain, or spondylosis or

spondylolysis/spondylolisthesis (the major criterion of arthralgia and this criterion are mutually

exclusive).

Dislocation/subluxation in more than one joint, or in one joint on more than one occasion.

Three of more traumatic or overuse injuries, such as epicondylitis, tenosynovitis, or bursitis).

Marfanoid habitus (table 1).

Abnormal skin: striae, hyperextensibility, thin skin, papyraceous scarring. The soft and silky texture

of the skin and the ability to stretch it more than might be found in a non-hypermobile person is

qualitative. This is best assessed by pulling the skin upward on the dorsum of the hand or over the

olecranon at the elbow (picture 2).

Eye signs: drooping eyelids, myopia, or antimongoloid slant (ie, a lateral downward slant or lateral

canthal dystopia).

Varicose veins, hernia, or uterine/rectal prolapse.



echocardiography, and fibrillin gene testing. (See "Genetics, clinical features, and diagnosis of Marfan syndrome

and related disorders", section on 'Criteria for diagnosis of MFS' and "Genetics, clinical features, and diagnosis

of Marfan syndrome and related disorders", section on 'Revised Ghent nosology'.)

Ehlers-Danlos syndrome EDS includes a group of conditions generally characterized by hyperelasticity and

fragility of the skin and by hypermobility of the joints. The distinction between JHS and EDS-hypermobility type

(EDS-HM, formerly termed EDS III) is subtle, if at all, and makes no difference to the management [5]. 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 or vascular collapse, the rarer variants

of EDS, including EDS classic type and EDS vascular type, should be considered [28]. The diagnosis of EDS,

other than EDS-HM, 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'.)

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.

These may include:

TREATMENT Treatment of patients with the joint hypermobility syndrome (JHS) should be individualized,

based upon the patients symptoms, clinical findings, and response to treatment interventions. Patients can

often be managed effectively by their primary care provider, who should coordinate the patients individualized

multidisciplinary care, including patient education regarding the condition, and referrals for physical and

occupational therapy and to medical and surgical specialists, depending upon the patients clinical

manifestations. (See 'Patient education and self-management' below and 'Musculoskeletal manifestations and

pain' below and 'Fatigue' below and 'Referral for associated manifestations' below.)

Patients for whom the diagnosis is uncertain or assistance is needed in overall management should be referred

to an expert in the management of patients with JHS, such as a rheumatologist or clinical geneticist. A clinical

geneticist can assist in confirming or excluding a diagnosis of another hereditary disorder of connective tissue

(eg, Marfan syndrome or Ehlers-Danlos of the classic or vascular type).

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.

Laboratory tests for myopathies; endocrinopathies; hematological disorders, including clotting

abnormalities; inflammation; and autoantibodies for autoimmune rheumatic disease may assist in

excluding other conditions suggested based upon clinical findings.

In patients with a heart murmur or those in whom Marfan syndrome is suspected, echocardiography

should be performed to determine if mitral valve disease or abnormalities of the aorta or aortic valve are

present. (See "Definition and diagnosis of mitral valve prolapse" 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 "Pathophysiology, clinical features, and evaluation of

chronic aortic regurgitation in adults".)

Patients with a history of low-trauma fracture should undergo bone mineral density testing to determine if

osteopenia or osteoporosis is present. (See "Screening for osteoporosis".)

Patients suspected of postural orthostatic tachycardia syndrome should be assessed clinically with

orthostatic pulse and blood pressure testing (increase in pulse of >30 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".)



Patient education and self-management All patients should receive education regarding the nature of the

condition, and we advise interested patients to seek further education, self-help, and supportive advice through

national organizations such as The Hypermobility Syndromes Association (HMSA), based in the UK [29], and

The Ehlers-Danlos National Foundation (EDNF), based in the US [30].

Musculoskeletal manifestations and pain We suggest that all patients undergo physical therapy for

assistance in the management of the musculoskeletal issues, including use of appropriate exercises, splints,

and adaptive devices. We refer patients to a physical therapist, when available, who has expertise in the care of

JHS and related conditions. Patients with significant upper extremity involvement or anatomic abnormalities

affecting the feet should be further evaluated and treated by an occupational therapist or podiatrist, respectively.

We also advise individual pain management using a multidisciplinary approach of the type advocated for patients

with fibromyalgia or chronic neuropathic pain. (See "Initial treatment of fibromyalgia in adults", section on

'Overview of treatment' and "Treatment of fibromyalgia in adults not responsive to initial therapies", section on

'Multidisciplinary treatment programs' and "Overview of the treatment of chronic pain", section on 'Neuropathic

pain'.)

Use of these strategies is based upon observational data, including case series; patient survey data; and the

experience of experts, including the authors [31-35]. However, there is a lack of randomized trials of these

approaches in patients with JHS [36].

Evidence for the effectiveness of this approach, including several of these interventions, was found in a survey of

Physical and occupational therapy and exercise Patients should participate in physical and

occupational therapy and exercise adapted for individuals with joint hypermobility to improve joint stability

and strength, avoid injury, and help overcome physical concerns [31-35]. The approach in patients with

JHS is a global view with a focus on joint protection, muscular rebalancing, strengthening, and joint

stabilization, rather than an isolated view of one joint or body region. Physical therapies should take

account of the individuals normal range of joint movement, joint instability, risk of soft tissue injury, and

poor proprioception. Therapies that may be of benefit include physiotherapy, occupational therapy, and

exercise program such as Pilates and Tai Chi.

Splints and orthoses We use orthotics and splints for improving joint alignment and providing stability

in conjunction with physical and occupational therapy and podiatry evaluation.

Chronic widespread pain The treatment of chronic widespread pain, which should be individualized in

patients with JHS, is the same as for other conditions with highly similar manifestations, such as

fibromyalgia syndrome [16]. Pharmacologic treatments may include simple analgesics, such as

acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs); and patients may benefit from the use of

selected antidepressants, antiseizure medications, and muscle relaxants that are of benefit in the

management of chronic pain. Patients may benefit from multidisciplinary pain management programs,

including cognitive behavioral therapy. These treatments are described in detail separately. (See "Initial

treatment of fibromyalgia in adults" and "Treatment of fibromyalgia in adults not responsive to initial

therapies".)

Patients who do not respond adequately to initial measures for pain management should be referred to

specialists in pain management and clinical psychology, and where possible to experts in the use of

cognitive behavioral therapy. (See "Overview of the treatment of chronic pain".)

Treatments for pain appear similarly effective in JHS compared with other chronic pain syndromes, both in

our experience and that of other experts [16]. There are no randomized trials that have evaluated such

interventions in patients with JHS.

Anxiety and depression Patients with mood disorders, such as anxiety and/or depression, which may

be associated with chronic pain, should be evaluated and managed by experts in the treatment of these

conditions. Where possible, such management should be incorporated into multidisciplinary pain

management programs. (See "Overview of the treatment of chronic pain", section on 'Concurrent

depression' and "Pharmacotherapy for generalized anxiety disorder" and "Unipolar major depression in

adults: Choosing initial treatment".)



patients regarding their perception of the degree of benefit obtained from different strategies [37]. Responses

were reported on a scale of 0 to 10, where 0 was completely ineffective and 10 was complete effective. Patients

reported the following regarding each of the treatments indicated:

Fatigue The potential causes of fatigue in a given patient should be identified and individually addressed.

Underlying metabolic or hematological causes should be managed accordingly. Otherwise, the management of

fatigue in JHS is primarily the management of pain, sleep patterns, and autonomic dysfunction. (See

'Musculoskeletal manifestations and pain' above and "Approach to the adult patient with fatigue" and 'Referral for

associated manifestations' below.)

Patients with fatigue who are suspected of an endocrine/metabolic disorder (eg, hypothyroidism,

hypoadrenalism) as a potential cause for such symptoms may require referral to an expert in endocrinology.

Referral for associated manifestations Additional referrals depend upon the clinical manifestation. The

management of systemic manifestations associated with JHS is generally the same or very similar to usual

management for these conditions in patients who do not have JHS or joint hypermobility (JHM). The

management of some of these disorders is described in detail separately. Conditions that may require further

referral may include:

Analgesics Scores of at least 5/10 and at least 7/10 were reported by 70 and 35 percent, respectively.

Pain management/coping strategies Scores of at least 5/10 and at least 8/10 were reported by 70 and

45 percent, respectively.

Physical therapy Scores of at least 5/10 and at least 8/10 were reported by 65 and 30 percent,

respectively.

Self-exercise and education Scores of at least 5/10 and at least 8/10 were reported by 60 and 30

percent, respectively.

Pilates Scores of at least 5/10 and at least 8/10 were reported by 85 and 55 percent, respectively.

Overall improvement in wellbeing Improvements in function and ability to cope with their condition were

reported in 55 percent, and a further 25 percent reported stability at the same level of disability following

treatment interventions.

Patients with orthostasis or other symptoms suggesting cardiovascular disease or autonomic dysfunction

should be referred to a specialist in these areas (see "Mechanisms, causes, and evaluation of orthostatic

hypotension" and "Treatment of orthostatic and postprandial hypotension" and "Postural tachycardia

syndrome"). Patients suspected of a cardiac anomaly should also be referred to an expert in

cardiovascular disease.

Patients with symptoms of bowel dysmotility or other gastrointestinal disturbance, including rectal

prolapse, should be referred to an expert in gastroenterology for evaluation and assistance in

management. Irritable bowel syndrome is managed as described separately. (See "Clinical manifestations

and diagnosis of irritable bowel syndrome in adults" and "Treatment of irritable bowel syndrome in adults"

and "Overview of rectal procidentia (rectal prolapse)".)

Patients with bladder dysfunction or interstitial cystitis should be referred to an expert in urology or

urogynecology. The management of these disorders is described in detail separately. (See "Pathogenesis,

clinical features, and diagnosis of interstitial cystitis/bladder pain syndrome" and "Evaluation and

diagnosis of bladder dysfunction in children" and "Management of interstitial cystitis/bladder pain

syndrome" and "An overview of the epidemiology, risk factors, clinical manifestations, and management of

pelvic organ prolapse in women".)

Patients with easy bruising or those in whom there is a question of whether a coagulation disorder is also

present should be referred to a hematologist with expertise in the evaluation and treatment of bleeding

disorders. (See "Approach to the child with bleeding symptoms" and "Approach to the adult patient with a

bleeding diathesis".)



PROGNOSIS The long-term prognosis of the joint hypermobility syndrome (JHS) has not been

systematically examined, but several features have been associated with an adverse prognosis in our clinical

experience. These include pain on cervical spine movements, particularly extension; neurologic symptoms,

especially severe paresthesia in all four limbs induced by cervical movement; and symptoms of autonomic

dysfunction, such as dizziness, faintness, pre-syncope or syncope, tachycardia, or problems with temperature

regulation.

Joint laxity decreases with age. This may result in less injury. There have been no longitudinal studies exploring

the association with either early-onset or progressive osteoarthritis.

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 5 to 6 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 10 to 12 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.)

SUMMARY AND RECOMMENDATIONS

Patients with muscle weakness or pain suspected of a myopathy should be referred to an expert in

muscle disease, such as a neurologist or rheumatologist. (See "Approach to the patient with muscle

weakness" and "Approach to the patient with myalgia".)

Patients with symptomatic spinal instability should be evaluated by an expert in the treatment of such

disorders, such as a neurosurgeon. The major symptoms indicating a need for consultation are the

reproducible exacerbation or precipitation of autonomic and or neurological symptoms, such as autonomic

dysfunction or pain, when the cervical spine is moved in certain directions. For example, intermittent

cervical cord compression can be suggested by symptoms that occur with extension or hyperextension of

the cervical spine [38]. The evaluation of such patients may include magnetic resonance imaging (MRI) of

the cervical spine and base of the skull with the neck in extension to determine whether cord compression

and low-grade Chiari-1 malformations are present [39]. Dynamic upright MRI of the cervical spine with

flexion/extension views may reveal significant craniocervical instability responsible for inducing transient

dysfunction of the cervical cord and extensive autonomic nervous system dysfunction.

th th

th th

Basics topic (see "Patient information: Ehlers-Danlos syndrome (The Basics)")

The joint hypermobility syndrome (JHS) is the most common disorder among the hereditary disorders of

connective tissue, affecting a subset of the 10 to 20 percent of the general population with joint

hypermobility. The precise prevalence is unknown. JHS is indistinguishable from, if not identical to, the

most common variant of Ehlers-Danlos syndrome (EDS), EDS-hypermobility type (EDS-HM), but the

precise relationship between EDS-HM and JHS remains uncertain, and 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 JHS. (See 'Epidemiology' above and 'Pathophysiology' above.)

The major clinical features of the JHS include symptoms and findings related to the musculoskeletal and

skin changes, including joint hypermobility (JHM), fragility of skin and supportive connective tissues, and

some features common to other hereditary disorders of connective tissue (HDCT). Additionally, systemic

features are often present, including chronic widespread pain, fatigue, autonomic dysfunction, and

gastrointestinal dysmotility. (See 'Clinical manifestations' above.)

The diagnosis of JHS is made clinically, based upon the medical history and physical examination, using

the Brighton 1998 criteria for JHS (table 2), which describes the combinations of musculoskeletal and

other historical and clinical findings that may be used to make the diagnosis; there are no diagnostic



ACKNOWLEDGMENT The editorial staff at UpToDate, Inc. would like to acknowledge Dr. Robert Sheon, who

contributed to an earlier version of this topic review.

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REFERENCES

1. Grahame R. Hypermobility: an important but often neglected area within rheumatology. Nat Clin PractRheumatol 2008; 4:522.

2. Hakim AJ, Grahame R. High prevalence of joint hypermobility syndrome in clinic referrals to a NorthLondon community hospital. Rheumatology 2004; 43 suppl 1:198.

3. Mulvey MR, Macfarlane GJ, Beasley M, et al. Modest association of joint hypermobility with disabling andlimiting musculoskeletal pain: results from a large-scale general population-based survey. Arthritis CareRes (Hoboken) 2013; 65:1325.

4. Fikree A, Aziz Q, Grahame R. Joint hypermobility syndrome. Rheum Dis Clin North Am 2013; 39:419.

5. Tinkle BT, Bird HA, Grahame R, et al. The lack of clinical distinction between the hypermobility type ofEhlers-Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome). Am JMed Genet A 2009; 149A:2368.

6. Hakim AJ, Cherkas LF, Grahame R, et al. The genetic epidemiology of joint hypermobility: a population

laboratory tests for JHS. A component of the Brighton criteria is ascertainment of the Beighton score for

JHM (table 3), which should be evaluated in all patients suspected of JHS. (See 'Diagnosis' above and

'Brighton criteria for JHS diagnosis' above and 'Beighton score for joint hypermobility' above.)

The differential diagnosis for JHS includes the conditions that have generalized joint hypermobility as a

clinical feature, particularly Marfan syndrome and EDS, other than EDS-HM. (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.)

Treatment of patients with JHS should be individualized based upon the patients symptoms, clinical

findings, and response to treatment interventions. Patients should receive education regarding the nature

of the condition, and pain management should employ a multidisciplinary approach. (See 'Treatment'

above and 'Patient education and self-management' above and 'Musculoskeletal manifestations and pain'

above.)

We suggest that all patients undergo physical therapy rather than providing education or self-management

strategies alone (Grade 2C). Whenever available, the physical therapist should have expertise in the care

of JHS and related conditions. The therapist can provide assistance in the management of the

musculoskeletal issues, including use of appropriate exercises, splints, and adaptive devices. Patients

with significant upper extremity involvement or anatomic abnormalities affecting the feet should be further

evaluated and treated by an occupational therapist or podiatrist, respectively. (See 'Musculoskeletal

manifestations and pain' above.)

The management of systemic manifestations associated with JHS is generally the same or very similar to

usual management for these conditions in patients who do not have JHS or JHM. Conditions that may

require further referral include bowel dysmotility or other gastrointestinal disturbance, orthostasis or other

symptoms suggesting cardiovascular disease or autonomic dysfunction, bladder dysfunction or interstitial

cystitis, easy bruising or other findings suggesting coagulation disorder, muscle weakness or pain

suggestive of a myopathy, and symptomatic spinal instability. (See 'Referral for associated manifestations'

above.)



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Topic 5591 Version 10.0



GRAPHICS

Joint laxity

Laxity of the wrist allows approximation of the thumb to the patient's

ipsilateral forearm. Joint laxity is a crucial feature of the hypermobility

syndrome.

Reproduced with permission from Sheon RP, Moskowitz RW, Goldberg VM. Soft

Tissue Rheumatic Pain: Recognition, Management, Prevention, 3rd ed,

Williams & Wilkins, Baltimore 1996.

Graphic 61525 Version 2.0



Elbow hypermobility

Laxity of the elbow with greater than 10 degrees of joint extension.

Reproduced with permission from: Sheon, RP, Moskowitz, RW, Goldberg, VM.

Soft Tissue Rheumatic Pain: Recognition, Management, Prevention, 3rd ed.





Knee hypermobility

Laxity of the knee with greater than 10 degrees of joint extension.

Reproduced with permission from Sheon, RP, Moskowitz, RW, Goldberg, VM.

Soft Tissue Rheumatic Pain: Recognition, Management, Prevention, 3rd ed,





Spinal hypermobility

While keeping the knees locked straight, the person with joint laxity

can bend and lay palms to floor.

Courtesy of Robert Sheon, MD.




Characteristics of the Marfanoid habitus

Name of

measurement

Value consistent

with Marfanoid

habitus*

Technique for measurement and

for calculation of ratio

Span/height ratio >1.03 The span/height ratio (S-HR) is measured

by asking the patient to stand with their

back to a wall and in contact with the wall,

with the arms out to 90 degrees at the

shoulder, and hands and fingers fully

extended. The arm span is the measure

from the tip of the middle finger of one hand

to that of the other. This is then divided by

the height to obtain the S-HR.

Hand/height ratio >0.11 The hand/height ratio (H-HR). Hand length

is taken to be the distance between the

distal palmar crease to the tip of the middle

finger. This is then divided by the height to

obtain the H-HR.

Foot/height ratio >0.15 The foot/height ratio (F-HR). Foot length is

taken to be the distance between the base

of the posterior edge of the heel and the tip

of the hallux. This is then divided by the

height to obtain the F-HR.

Upper

segment/lower

segment ratio



Clinical assessment of skin hyperextensibility

Skin hyperextensibility can be assessed using the "rubber glove test"; as the skin fold is

gently pulled away from the skin surface, the true nature of the stretching process can be

observed. In the joint hypermobility syndrome or the hypermobility type of Ehlers-Danlos

syndrome, the characteristic finding is that the whole skin over the dorsal aspect of the

hand (up to and beyond the wrist in some cases) is seen to take part in the stretching

process as if the patient's skin were a rubber glove. In a normal individual, skin is seen

to stretch to a lesser degree and only in the region adjacent to where the fold is raised.

Courtesy of Rodney Grahame, MD.




Revised diagnostic criteria for the benign joint hypermobility

syndrome*

Major criteria

1. Beighton score of 4/9 or greater

2. Arthralgia for more than 3 months in 4 or more joints

Minor criteria

1. A Beighton score of 1, 2 or 3/9 (0 to 3 if over age 50)

2. Arthralgia for 3 months or more in 1-3 joints, or back pain for 3 months or more, of

spondylosis, spondylolysis, or spondylolisthesis

3. Dislocation or subluxation in more than one joint, or in one joint on more than

one occasion

4. Soft tissue rheumatism in 3 or more locations (eg, epicondylitis, tenosynovitis, bursitis)

5. Marfanoid habitus

6. Abnormal skin (eg, striae, hyperextensible, thin, or papyraceous scarring)

7. Eye abnormalities (eg, drooping eyelids, myopia, anti mongoloid slant)

8. Varicose veins or hernia or uterine/rectal prolapse

* Benign hypermobility syndrome is diagnosed when two major, one major and two minor, or

four minor criteria are present. The disorder is excluded in those with Marfan or Ehlers-Danlos

syndrome.

From Grahame, R, Bird, HA, Child, A, et al. J Rheumatol 2000; 27:1777.




Beighton score for joint laxity*

Specific joint laxity Left Right

Passive apposition of thumb to forearm 1 1

Passive hyperextension of fingers 1 1

Active hyperextension of elbow >10 degress 1 1

Active hyperextension of knee >10 degrees 1 1

Ability to flex spine and place palms to floor without bending knees 1

* This score is based upon joint laxity of the above nine anatomic sites. It is calculated by

adding all points, with nine being the highest total possible score. A score of four or higher is

generally considered an indication of generalized joint laxity.




The five-part questionnaire for identifying hypermobility

1. Can you now (or could you ever) place your hands flat on the floor without bending

your knees?

2. Can you now (or could you ever) bend your thumb to touch your forearm?

3. As a child, did you amuse your friends by contorting your body into strange shapes OR

could you do splits?

4. As a child or teenager, did your shoulder or kneecap dislocate on more than one

occasion?

5. Do you consider yourself double-jointed?

Patients who answer "yes" to two or more questions may be suspected of generalized joint

hypermobility.




Disclosures: Rodney Grahame, MD Nothing to disclose. Alan J Hakim, BA MB BChir Nothing to disclose. Peter H Schur, MDNothing to disclose. Paul L Romain, MD Employee of UpToDate, Inc.

Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are addressed by vettingthrough a multi-level review process, and through requirements for references to be provided to support the content. Appropriatelyreferenced content is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

Disclosures

joint hypermobility syndrome

Documents

diagnosis of marfan

edshypermobility type

thestickler syndrome

management of ehlers

clinical genetics

common variant of ehlers

ehlersdanlos syndromeseds

clinical features anddiagnosis