Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
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
Authors
Rodney Grahame, MD
Alan J Hakim, BA MB BChir
Section Editor
Peter H Schur, MD
Deputy Editor
Paul 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
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
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)
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
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)
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).
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".)
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".)
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".)
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
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.)