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'The Hypermobility Syndrome'

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'The Hypermobility Syndrome' Annals ofthe Rheumatic Diseases 1990; 49: 190-200 199 REVIEW ARTICLE Ann Rheum Dis: first published as 10.1136/ard.49.3.199 on 1 March 1990. Downloaded from 'The hypermobility syndrome' R Grahame The hypermobility syndrome is characterised Generalised joint laxity is a feature common by the occurrence of musculoskeletal symptoms to a wide variety of heritable disorders of in hypermobile subjects in the absence of connective tissue, many of which are rare. By demonstrable systemic rheumatological disease. contrast the hypermobility syndrome, as seen in When the syndrome was originally described in clinical practice, is a common finding. A diag- 19671 many rheumatologists viewed it with nostic survey of 9275 new referrals to one large some scepticism-more as a clinical curiosity general rheumatology clinic showed that the than a rheumatic disease. For one thing doctors syndrome was diagnosed more often than anky- and others are trained to examine for reduction losing spondylitis, crystal synovitis, or psoriatic of joint mobility rather than for an increased arthritis, comprising 3-25% of all female and range, so that hypermobility is commonly 0-63% of all male referrals.7 missed. Secondly, the absence of laboratory These patients present with a wide variety of abnormalities robbed the condition of scientific readily identifiable traumatic and overuse plausibility. Thirdly, there were no agreed lesions, such as traction injuries at tendon or criteria for hypermobility, merely a rather crude ligament insertions, joint or tendon sheath set of diagnostic manoeuvres, which have come synovitis, chondromalacia patellae, rotator cuff to be known as the Beighton criteria.2 It is very lesions, or back pain due to soft tissue injury or much to its credit that despite criticism over the disc prolapse. Others suffer the effects of joint years, and despite various attempts to develop instability, suchas flat feet, recurrent dislocation, more sophisticated devices, the nine point scale or subluxation-notably of the shoulder patella, has withstood the test of time and remains the metacarpophalangeal joints, or temporo- universally adopted yardstick for clinical and mandibular joints. Others still, develop a epidemiological studies. chronic arthritis-either a low grade inflam- To what extent has our knowledge and matory synovitis of traumatic origin (which may understanding of this condition advanced over mimic and be consequently misdiagnosed as http://ard.bmj.com/ the past 22 years? The encouragingly large rheumatoid or juvenile chronic arthritis) or number of scientific contributions published osteoarthritis, which is held by many authorities from many countries and ranging over clinical, (albeit on circumstantial evidence) to be a epidemiological, and basic scientific aspects direct complication of the hypermobility syn- attest to the substantial progress made in the drome.8 What sets the patient with the hyper- understanding of this group of disorders. mobility syndrome apart from other rheuma- Generalised ligamentous laxity, the pre- tology clinic attenders is the profusion and requisite of joint hypermobility, is seen in a spectrum of common lesions occurring in the on September 23, 2021 by guest. Protected copyright. substantial proportion of healthy individuals same individual and often spanning his (or more (varying according to methodology and to the commonly her) whole lifetime.9 More difficult age, sex, and ethnic origin of the population to explain in such patients is the commonly studied), the overwhelming majority of whom encountered arthralgia or myalgia in the absence probably suffer no ill effects. On the contrary, of any demonstrable clinical abnormality. One many derive added advantage in their pursuit of postulated mechanism is the overstimulation of such activities as athletics, acrobactics, and ballet nociceptive nerve endings, which are poorly dancing, where greater flexibility is an asset.3 supported by defective collagen fibrils.'0 Mobility for a given joint follows a Gaussian Evidence has emerged from many centres distribution,4 and within a population it is that extra-articular organs and tissues, which generally those subjects whose joint range is rely for their structural integrity on the tensile more than two standard deviations above the strength of normal collagen, may also become mean who suffer musculoskeletal symptoms.5 disordered in hypermobile subjects. The skin Hypermobility diminishes markedly through- may be thin, soft, hyperextensible, and develop out childhood and then more slowly during striae. Fifty eight per cent of patients in one adult life. Women generally show a greater joint series showed such skin changes, and a charac- range than men, and Asians a greater range than teristic facies has been described.'0 An associa- Negroes, who in turn are more mobile than tion between mitral valve prolapse and the Caucasians. A recently established fact is that hypermobility syndrome (and vice versa) has 'pauciarticular hypermobility' is even more been reported in studies in the United prevalent in otherwise healthy subjects than the Kingdom" and in Czechoslovakia,'2 and an Department of generalised variety. Among 660 North American increase in aortic compliance has been Rheumatology, Guy's Hospital, music students of all ages 47% of the men and recorded.'3 Weakness of the musculotendinous London SEI 78% of the women showed at least one hyper- supporting structures of the anterior abdominal R Grahame mobile joint.6 wall and pelvic floor no doubt explains the 200 Grahame reported increased finding of abdominal examination of the same samples showed abnor- hernia,'4 and of both rectal'5 and uterine small fibrils with an increase in mally collagen Ann Rheum Dis: first published as 10.1136/ard.49.3.199 on 1 March 1990. Downloaded from prolapse'6 in subjects with hypermobility syn- interfibrillar matrix, elastin, and fibrocytes. drome. Bone fragility may also be present, Studies of family pedigrees9 10 have provided resulting in an increased liability to fracture." evidence for a dominant mode of inheritance Stress fractures of the metatarsal bones and of with sex-influenced phenotypic manifestations the vertebral bodies and partes interarticulares in most cases of the hypermobility syndrome. of the lumbar spine are particularly common, Within individual families women are more the latter constituting additional potential commonly and more severely affected than sources of low back pain in the hypermobility men, with a different phenotype pattern. syndrome. Another manifestation of bone Women tend to present with arthralgia and softening seen in the syndrome is idiopathic mitral valve prolapse, whereas men tend to protrusio acetabulae."' An additional feature, develop dislocations, back pain, or torn menisci the marfanoid habitus, has also been described or tendons. in patients with the hypermobility syndrome. In Although there have been recent exciting one series 39% were found to have a marfanoid discoveries using molecular genetic techniques habitus (defined as an upper segment:lower in many disorders, including variants of osteo- segment ratio of <0 89) compared with 11l5% genesis imperfecta and the Ehlers-Danlos syn- of controls (p<0 05)." drome,'9 the application of such techniques to It was this constellation of clinical abnor- unravelling the mysteries of the hypermobility malities observed in hypermobile subjects that syndrome is still in its infancy. Preliminary gave rise to the hypothesis that the hypermobility work in selected families with hypermobility syndrome was a forme fruste of a heritable syndrome using the technique of segregation disorder of connective tissue-a (mercifully) analysis suggests that the syndrome is not benign overlap syndrome which incorporated caused by a mutation involving collagen types I many of the features seen in the rarer classical or III, nor the a-2 chain of type V or the a-3 hereditary disorders such as the Marfan syn- chain of type VI (Brothertom, Child, Grahame, drome, the Ehlers-Danlos syndrome, and osteo- Henney, unpublished data). genesis imperfecta. A panel of 21 expert geneticists from 10 countries has recently drawn up an agreed comprehensive classification of the many syn- 1 Kirk J H, Ansell B A, Bywaters E G L. The hypermobility dromes and variants of syndromes that have syndrome. Ann Rheum Dis 1967; 26: 419-25. 2 Beighton P H, Solomon L, Soskolne C. Articular mobility in been published ('The Berlin nosology'). 8 Unfor- an african population. Ann Rheum Dis 1973; 32: 413-8. tunately, the patients with hypermobility syn- 3 Grahame R, Jenkins J M. Joint hypermobility-Asset or liability? Ann Rheum Dis 1972; 31: 109-11. drome described above as commonly displaying 4 Wood P H N. Is hypermobility a discrete entity? Proceedings overlap features (marfanoid habitus, mitral of the Royal Society ofMedicine 1971; 64: 690-2. 5 Pouk J, Fait M. Frequency of occurrence of generalised http://ard.bmj.com/ valve prolapse, skin hyperextensibility, and ligamentous laxity in a population of children. Reumatologia joint laxity) do not fit comfortably into the (USSR) (in press). 6 Larsson L-G, Baum J, Mudholkar G S. Hypermobility: Berlin nosology. Neither of the two nearest features and differential incidence between the sexes. designations, the Ehlers-Danlos syndrome III Arthritis Rheum 1987; 30: 1426-30. 7 Grahame R. Clinical manifestations of the joint hypermobility (hypermobile type) and the familial articular syndrome. Reumatologia (USSR) 1986; 2: 20-4. hypermobility
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