|Year : 2016 | Volume
| Issue : 1 | Page : 12-18
Benign joint hypermobility syndrome
Nirankar Singh Neki, Ajay Chhabra
Department of Medicine, Government Medical College, Amritsar, Punjab, India
|Date of Web Publication||4-Mar-2016|
429, Akash Avenue, Fatehgarh Churian Road, Amritsar - 143 001, Punjab
Source of Support: None, Conflict of Interest: None
Benign hypermobility joint syndrome or benign joint hypermobility syndrome (BJHS) is a common yet poorly recognized disorder of joint in children and adults. It is a connective tissue disorder which affects musculoskeletal system in the absence of general rheumatologic features. Benign hypermobility is stated as laxity of joints that may be associated with pain, discomfort after exercise, and even recurrent subluxations. People with this condition generally report prolonged pain and poor exercise tolerability. The term "benign" has been used to separate BJHS from other hereditary connective tissue disorders that besides having a common denominator of joint hypermobility also involve other organs such as the eyes, bones, heart, and blood vessels. Management includes early recognition keeping a high degree of suspicion using Brighton's criteria. Treatment includes patient education, modification of activity and physiotherapy along with anti-inflammatory agents in case of severe joint infliction.
Keywords: Benign, Brighton′s criteria, joint hypermobility syndrome
|How to cite this article:|
Neki NS, Chhabra A. Benign joint hypermobility syndrome. J Mahatma Gandhi Inst Med Sci 2016;21:12-8
| Introduction|| |
"Hypermobility syndrome" term was coined by Kirk in 1967.  Joint hypermobility syndromes include various disorders like benign hypermobility syndrome, Ehler-Danlos syndrome (EDS), Marfan's disease, and osteogenesis imperfect which are classified under hereditary connective tissue disorders (HCTDs).  Benign joint hypermobility syndrome (BJHS), unlike other disorders, does not have ocular, cardiac, and skin manifestations. HCTDs are differentiated on the basis of clinical features, other systemic features besides joint laxity and molecular diagnostic techniques.  BJHS is a disorder of hypermobility of joints affecting primarily musculoskeletal syndrome without systemic rheumatologic features. Morbidity associated with BJHS is due to the involvement of musculoskeletal system only and it does not directly lead to joint destruction or permanent disability. It is likely to be an inherited disorder. 
Adequate methods for measuring the range of movement at joints are essential for the definition of criteria used in the study of clinical problems associated with joint hypermobility. The definition of "generalized joint hypermobility" still remains arbitrary, and rationally should reflect both the number of joints involved and the extent to which they move along with the exclusion of HCTDs.  Various criteria used to diagnose BJHS are Beighton's scoring system,  Carter Wilkinson criteria,  and Brighton's criteria. The latter seems to be most reproducible. 
| Epidemiology|| |
Generalized joint laxity is commonly seen in healthy individuals who do not have complaints. The incidence in school going children may be as high as 40%.  Hypermobility that is not associated with systemic disease occurs in 4% to 13% of the population.  In a study, it was shown to be prevalent in 11.7%.  It also appears to vary with sex and race. Females are generally more mobile than males of the same age group. , Mobility decreases with advancing age.  It was seen in 16% female students versus only 7% of males.  There are noticeable racial differences in joint mobility among normal populations. Indians are more mobile than blacks, and blacks in turn are more mobile than Caucasians. , People of Asian, Middle Eastern, and African descent have increased joint laxity as compared to Europeans and Americans. , In a study done on Iranian army, recruits showed that joint hypermobility was seen in 29.4% which is relatively very high as compared to what the current data suggests.  One study found that hypermobility occurred in 66% of school children presenting to rheumatologists with arthralgia of unknown etiology.  Hypermobility occurs in several HCTDs like Marfan syndrome, EDS, osteogenesis imperfect, in chromosomal disorders like Down's syndrome and in inborn errors of metabolism like homocystinuria and hyperlysinemia. Recurrent dislocation of the shoulder and patella may be associated with hypermobility syndrome. Juvenile rheumatoid arthritis may also lead to joint laxity along with other extra-articular manifestations. BJHS is likely to be genetically heterogeneous, and candidate genes are under investigation. One such gene encoding for tenascin-X is being studied whose prevalence is 5-10% in BJHS. 
| Clinical Manifestations|| |
Most patients are asymptomatic. Children who have hypermobility syndrome may present with a variety of musculoskeletal complaints.  The most common symptom is joint pain, which develops after physical activities or sports during which the affected joints are subjected to extremes of movement repeatedly. Pain may be localized in one or several joints or around it. Since symptoms typically are related to activity, they tend to occur in the latter half of the day. Patients may awaken at night with complaints of joint or extremity pain, especially following daylong activity. Pain is mostly self-limiting but may tend to be more persistent by the passing years.  In contrast to arthritic disorders; morning stiffness is not a feature of hypermobility syndrome. At times, hypermobility syndrome may involve the joints symmetrically and falsely mimic systemic arthritides. Patients may also experience joint stiffness, myalgias, muscle cramps, and nonarticular limb pain. Although pain most commonly involves the knee, ankle, elbow, and joints of hand (especially in musicians), any joint can be affected. Although brief episodes of joint swelling can occur in hypermobility syndrome, the presence of acute symmetrically tender joints should prompt reconsideration of the diagnosis. 
The term "double jointed" is often used as a synonym for hypermobility. However, the name is a misnomer and should not be taken literally as hypermobile joints are not double or anatomically different in any way, and it may tend to run in families with cousins being affected as well. It is often described in families of contortionists who utilize their condition for a living. In addition to relatively nonspecific musculoskeletal complaints, some patients may have an associated history of recurrent joint dislocations or subluxations, ligament or tendon rupture, especially those who indulge in sports. Physical examination may reveal pain and inflammation of joints besides the findings suggestive of joint hypermobility. Signs of severe inflammation like marked tenderness, swelling, redness, warmth, and fever are usually absent. If such findings are present, they suggest a different diagnosis.
Examination of patients who have hypermobility syndrome also may reveal extra-articular abnormalities that are more typical of other hereditary connective tissue disorders. Such findings can include pes planus, scoliosis, lordosis, genu valgum, lateral patellar displacement, marfanoid habitus, high-arched palate, skin striae, thin skin, and varicose veins. Although most affected children do not have cardiovascular findings, a subset of patients may have evidence of mitral valve prolapsed (MVP).  The association of MVP with hypermobility syndrome is controversial. Although early studies indicated an increased incidence of MVP in affected patients, more recent investigations that used rigorous echocardiographic criteria for the diagnosis of MVP have questioned this association. Serious cardiovascular abnormalities may be more prevalent in other connective tissue disorders that also manifest with hypermobility like Marfan's syndrome and EDS.  In a study conducted by Mishra et al., MVP was seen in 10% of patients of BJHS as compared to controls who exhibited an incidence of 7%.  For this reason, any hypermobile child who has suspicious cardiac symptoms or physical findings requires further evaluation by a cardiologist and a geneticist.
| Diagnosis|| |
Joint hypermobility is a phenotypic feature common to various heritable disorders like EDS and Marfan's syndrome and BJHS. Joint hypermobility can be recognized using five simple clinical maneuvers that require no special instruments and can be performed by a clinician quickly. These criteria were first developed by Carter and Wilkinson  and later modified by Beighton, Solomon, and Soskolne, which popularly are referred to as Beighton's criteria.  The five clinical maneuvers for screening joint hypermobility as laid under Beighton's scoring system are shown in [Table 1] and [Figure 1] [Figure 2] [Figure 3] [Figure 4] [Figure 5].
|Figure 1: Forward flexion of trunk with knees extended and hands touching the floor|
Click here to view
A score of 4/9 is taken as a positive marker of joint hypermobility.  A general physician can easily apply these criteria to diagnose patients with generalized joint laxity. On this subset of patients, Brighton's criteria are applied to diagnose patients of BJHS. Brighton's criteria,  which incorporate Beighton's scoring system, help distinguish patients of BJHS from other connective tissue disorders [Table 2].
All said and done BJHS is a diagnosis of exclusion. A complete workup to rule out other disorders is necessary. A comprehensive panel of tests should be done to exclude systemic inflammatory musculoskeletal disorders, and molecular diagnostic tests should be performed where specific HCTDs are posing as a difficult differential. Joint effusions, if present, are mild, and aspiration shows a noninflammatory pattern.
| Differential Diagnoses|| |
Various differentials have been discussed in [Table 3] which include some heritable diseases, metabolic diseases, orthopedic disorders, and certain acquired diseases. BJHS has to be especially differentiated from other disorders known as heritable disorders of connective tissue like EDS, Marfan's syndrome, and Stickler syndrome which also manifest with joint hypermobility. ,
EDS refers to a group of 10 different inherited connective tissue disorders that shares the features of joint hypermobility, skin, and blood vessel abnormalities. Skin abnormalities include hyperstretchability, velvety, and easily bruisable. Blood vessel abnormalities include large vessel aneurysms that may rupture and lead to fatality. Diagnosis of EDS depends on major criteria which include:
EDS phenotype considerably overlaps with BJHS but presence of extra-articular involvement of eyes, major vessels, papery thin scars, the absence of sublingual, and inferior labial frenula. Especially, the familial hypermobile form which is seen in 10% may be difficult to differentiate from BJHS. ,,
- Beighton score of 5/9.
- Skin involvement (hyperextensibility and/or smooth, velvety skin) and minor criteria including.
- Recurring joint dislocations.
- Chronic joint/limb pain.
- Positive family history along with molecular confirmatory tests.
Marfan syndrome is an autosomal dominant disorder caused by FBN1 gene mutation on chromosome 15 characterized by a tall thin body habitus, long extremities (dolichostenomelia), elongated fingers (arachnodactyly), ocular abnormalities (myopia, ectopia lentis), thoracolumbar abnormalities (pectus excavatum, pectus carinatum, and scoliosis), and generalized joint hypermobility. The patient should undergo cardiologic and ophthalmologic, as well as genetic evaluation. 
Osteogenesis imperfecta, an autosomal dominant disorder of type 1 collagen (mutations in COL1A gene or COL2A gene on chromosome 17 and 2, respectively), is characterized by thin blue sclere, excessive joint mobility, growth retardation, and bone fragility often resulting in recurrent fractures and bony deformities. 
Williams syndrome is an autosomal dominant disorder involving mutations at ELN gene on chromosome 7q11.23 encoding for elastin. Joint laxity is observed primarily in childhood while older individuals develop joint contractures. These patients also manifest mental retardation, short stature, characteristic facial appearance, hernias, hoarse voice, delayed psychomotor skills, behavioral abnormalities, hypercalcemia, and cardiovascular abnormalities (most commonly supravalvular aortic stenosis). Definitive diagnosis is possible by genetic testing by fluorescent in situ hybridization. 
Stickler syndrome (hereditary progressive arthro-ophthalmopathy) is an autosomal dominant disorder that is characterized by hypermobility, typical facial features (malar hypoplasia with depressed nasal bridge and epicanthal folds), Pierre-Robin sequence (micrognathia, glossoptosis, and U-shaped cleft palate), early-onset arthritis, severe myopia, and sensorineural hearing loss. Affected infants often experience respiratory problems. Diagnosis is confirmed by genetic testing. 
Homocystinuria is an autosomal recessive metabolic disorder of methionine metabolism in which there is an excessive accumulation of homocystine and its metabolites. It is characterized by marfanoid body habitus, ectopia lentis, mental retardation, and generalized joint hypermobility. Patients are significantly at increased risk for arterial thrombosis. Screening tests include cyanide nitroprusside test and Guthrie's test. 
All these disorders can be clinically differentiated by the presence of a strong family history, extra-articular manifestations, characteristic facies, and habitus. However, genetic testing in the patient and affected siblings is required to confirm the diagnosis. Besides other acquired disorders can be differentiated on the basis of clinical manifestations and can be confirmed using laboratory investigations.
| Management|| |
Treatment for BHJS has to be individualized on the basis of his or her general health, previous medical history, the severity of pain or joint involvement, and the presence of other extra-articular manifestations. It includes:
The first and the most important part is in making the patient aware of his or her medical condition and telling the patient clearly that it is neither an inflammatory nor a progressive disorder. Patients should be enlightened regarding how to prevent joint injury. Educating and inculcating habits so that overstretching of the joints may be prevented. 
- Avoid squatting type of toilets.
- Avoid sitting cross-legged with both knees bent (Indian style).
- Place one foot over a pedestal when standing for long periods.
- Wear appropriate shoes with good arch and heel supports.
- Limit extreme movements of affected joints.
- Discourage the children to exhibit their hypermobility as a source of entertainment for others. ,,
As has already been discussed BJHS is not an inflammatory disease anti-inflammatory drugs have little role in treating or containing the disease. Joint pain and swelling after unaccustomed activity can be reduced with anti-inflammatory drugs such as naproxen, diclofenac, ibuprofen, or etoricoxib. Long-term use may lead on to cardiovascular side effects which are least with naproxen.  These are usually sufficient to relieve the discomfort as these complications are generally self-limiting. ,
Muscle strengthening and directed training programs can help the patient increase muscle mass and strength which in turn increases joint stability. Strengthening exercises and conditioning activities such as swimming, walking, and jogging help improve joint strength. Inactivity should be avoided as weight gain worsens the problems. Braces, splints, or bandaging may be advised to prevent injury to the affected joints during activity. ,,,
Appropriately designed physiotherapy regimes including local cold and hot fomentation, massage, short and long wave therapy, and ultrasonic therapy may alleviate pain and joint swelling.  It includes proprioceptive training so that an individual can sense and prevent extremes of joint mobility. 
Rarely, joint hypermobility may predispose to serious joint injury during extreme contact sports like lateral malleolar ligament tear, anterior cruciate ligament injury, meniscal tear, or rotator cuff injury. These conditions require urgent orthopedic attention and surgical intervention. 
As the name suggests, BJHS is a benign disorder which is noninflammatory and nonprogressive. However, patients should be educated about this disorder and the potential complications arising out of it. Children with lax joints often do well in activities that require flexibility such as gymnastics and dancing. However limiting some of these activities may be necessary if there is a history of recurrent arthralgias/arthritis, dislocation, or ligamentous injury. ,,
Most patients continue to suffer from joint and muscle pain from hypermobility as they age. They are at an increased risk of sprains, dislocations, subluxations, intermittent swelling, lumbago, and poor exercise tolerance. Individuals who have BJHS as adults are more likely to develop osteoarthritis or "wear and tear" arthritis with advancing age. ,
| Conclusion|| |
Pondering upon these facts it seems that this so-called "benign" disorder may not be so benign. This has led some authors to drop the prefix "benign" from BJHS and have re-christened it as "joint hypermobility syndrome" because of its long-term impact on the patients' lives. ,
At times, patients may be wrongly labeled as cases having inherited disorder with hypermobility. To prevent patient's agony of a misdiagnosis, various clinical and molecular studies should be used to differentiate various heritable disorders presenting with hypermobile joints from BJHS.  Further research is needed to understand hypermobility syndrome in a better way so that effective management strategies can be devised.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]