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Locomotor syndromes are frequent and troublesome in the Marfan syndrome [1, 2]. Close involvement with rheumatologists and orthopaedic surgeons may be indicated to manage painful joint hypermobility and its complications in early to mid-life, and, with increased longevity, degenerative joint disease in later years. Seventy per cent of children experience symptoms of arthralgia, back pain and ligament laxity and injury [1]. The earliest complaints of the child are often knee pain or ankle pain necessitating rest and analgesia. These symptoms, if not appreciated by parents and teachers, may lead to the belief that the child is not trying to participate in family outings or school sporting activities. It is important to allow the child to participate to the extent of his or her ability, but to permit rest, or to terminate the family outing, if the child cannot keep up. Taking a pushchair on family outings makes it a more pleasant activity for all concerned. Allowing the child to act as a referee or a goal keeper or play the least demanding role on the team at school is helpful. Weak ankles and knees, combined with poor eyesight may make the children appear clumsy in sporting activities, and they soon lose interest. It is important to wear sports shoes with ankle support, and even arch supports and heel cups, to render the gait more controlled. Ankle and knee supports may be worn to stabilise these joints, which are prone to recurrent sprains, and in some cases patellar dislocation. In severe cases, surgical fusion of the ankle, or shortening of the patellar ligaments may be helpful. Patients should be taught to gently reduce recurrent dislocations of patellae, fingers and toes. These joints gain stability with passing years. Wrist or finger splints may help to stabilise the loose wrist, thumb or fingers, and render writing neater. If the hand tires, especially during examinations, extra time should be given. Using fat pens or pencils, which may be built up, makes the handwriting more legible. For older children, the use of a laptop computer, or even a tape recorder to record lessons, may avoid the need for handwritten notes.

The ability of joints to undergo repeated and rapid movements is attributable to the unique mechanical properties of the extracellular matrix (ECM) of the joint capsule and surrounding ligaments and tendons. A delicate balance exists between ‘stiffness’ and ‘elasticity’ of these tissues. Stiffness comes from very long collagen fibrils that are arranged in elaborate architectures such as parallel bundles in tendon (Fig. 3.1), orthogonal lattices in the cornea and basket-weave in skin, depending on the mechanical requirements of the tissues in which they occur. Elasticity originates from the crimping of collagen fibrils and from elastic fibres in the ECM (Fig. 3.2). These elastic fibres have a unique arrangement of macromolecules that permits extension and contraction at a molecular level. An understanding of the molecular and structural basis of joint hypermobility requires a detailed knowledge of the structure, function and organisation of the collagenous and elastic polymer systems that comprise the ECM.

The first clinical description of articular hypermobility is attributed to Hippocrates, who, in the fourth century B.C., described the Scythians, a race of people inhabiting the region that now forms the Ukraine and Czechoslovakia, as having humidity, flabbiness and atony such that they were unable to use their weapons. Their main problem in warfare was that hyperlaxity of the elbow and shoulder joints prevented them from drawing their bows effectively.

This edition, the fourth in a series spanning some 25 years since the publication of the first edition in 1983, is likely to be the last prepared under the current authorship. In addition to chronicling further progress in the field, it seems appropriate to add a final chapter concerning areas that might be suitable, even ripe, for translational research in the future. This chapter, at times unashamedly speculative, synthesises the ideas of all three authors, each approaching the field from their slightly different perspectives. We apologise to readers if some of our suggestions prove impractical or if we have failed to consider their own areas of particular interest in this wide field.

Individuals endowed with hypermobility may excel in certain artistic occupations. The professional activities of ballet dancers, contortionists, musicians and sportsmen are all influenced by their range of joint movements. The wider implications of this situation are reviewed in this chapter.

A common clinical error is to confuse these two terms, which are not synonymous. Hypermobility is defined as an excessive range of joint motion, taking into consideration the age, gender and ethnic origin in otherwise healthy subjects, being greater in males than females, in younger people compared with older people and in those of Asian or African origin compared to those who are Caucasian. It is characterised by an inherent increase in laxity and fragility of the connective tissues. Hypermobility is a direct consequence of ligamentous laxity, which, itself, is an expression of a genetically determined aberration of one or more of the connective tissue fibrous protein genes such as those encoding for collagen(s), fibrillin(s) or tenascin(s)

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. Scoring systems for hypermobility that survey a large number of joints in simple fashion are ideal for epidemiological studies in large populations. Latterly, investigators have devised sophisticated mechanical devices for the precise quantification of movement at a single joint. The greater precision afforded may be ideal for serial assessments in the same patient but this greater precision is of limited use in epidemiological work if the joint fails to mirror the status of laxity at other joints in the body. Moreover, a joint may display acquired hyperlaxity in compensation for a reduced range of movement at adjacent joints, for example in the vertebral column.

Arguably, the most surprising development of the past decade has been the realisation that the effects of JHS do not lie exclusively within the confines of the musculoskeletal system. Nowadays, it is no exaggeration to state that JHS is seen as a multi-facetted multi-system disorder which effectively touches virtually all medical specialties in one way or another.

In an early paper, Sutro (1947) drew attention to the biomechanical aspects of hypermobility. In a study of recurrent effusions in the knees and ankles of American army recruits, he noted an increased range of both active and passive movement in the affected joints. He argued in favour of an “over-length” of certain articular, capsular and ligamentous tissues, and suggested that there might be disproportion in the relative rate of growth of the bones and their attached ligaments.

The heritable hypermobility syndromes are a group of disorders in which joint laxity is a prominent feature. In some of these conditions the loose joints predispose to a wide variety of articular complications and, despite their rarity, they are therefore of considerable rheumatological importance.

The following case histories have been drawn from the records of patients who have attended the Guy’s Hospital Hypermobility Clinic over the past two decades, many of whom have been observed over several years. A striking finding has been the number and variegated pattern of locomotor disorders suffered by individual patients. Many of the disorders encountered were amenable to treatment, and serious disablement was seen in only a few individuals. In each instance the Beighton et al. (1973) mobility scale was used.

The majority of persons with lax ligaments and loose joints suffer no articular problems. For example, rheumatic complaints were no more prevalent amongst a group of 31 healthy hypermobile blood donors (average age 28 years) than in age- and sex-matched controls (Jessee et al. 1980). For most hypermobile subjects it is a positive attribute which enables enhanced participation in a wide variety of physical activities (see Chap. 9). However, not all are so fortunate, and some experience locomotor and other problems as a direct result of their laxity. When symptoms result, the term hypermobility syndrome (HMS) is applied (Kirk et al. 1967). It must be emphasised that this designation is non-specific and in this context it does not denote any precise disease entity. Within an unselected group of 100 HMS patients, Finsterbush and Pogrund (1980) delineated three patterns of musculoskeletal complaint: (1) mild complaints of long duration, (2) acute episodes at various sites and (3) a combination of these.

The familial undifferentiated hypermobility syndromes are a heterogeneous group of disorders in which generalised joint laxity is the primary clinical manifestation. The Ehlers-Danlos syndrome (EDS) (Chap. 9) and other rare genetic conditions (Chap. 11) which have additional non-articular stigmata are excluded from this category.

The term hypermobility syndrome (HMS) was coined to denote the presence of rheumatic symptoms with generalised joint laxity, in the absence of any demonstrable systemic rheumatic disease (Kirk et al. 1967). Of 9275 consecutive patients attending the rheumatology clinic at Guy’s Hospital, 2% were diagnosed as suffering from HMS. Of these, 85% were female (see Chap. 6). A similar prevalence (1.7%) has been seen among 690 new referrals to a paediatric rheumatology centre (Ansell 1972).

The possible aetiology of joint hypermobility has become complicated in recent years. At one time a facile explanation sufficed; joint hyperlaxity, presumably related in some way to collagen structure, was regarded as an inherited abnormality explicable in terms of a simple, but at that stage undetermined, alteration in conventional collagen structure. However, in the last few years our understanding of hyperlaxity has increased considerably (Bird 1982), and any discussion on possible alteration of structure in hyperlax joints has to take into account the following observations: 1) The range of movement at a joint depends on several aetiological factors including the shape of the bone and cartilage (e.g. acetabular dysplasia), muscular power and tone and the laxity of the ligaments and joint capsule; 2) For any single joint, movements vary in Gaussian fashion throughout a population (Wood 1971); 3) There is probably ethnic variation; 4) Some individuals with hyperlax joints have connective tissue changes at other sites in the body which lead, for example, to floppy heart valves (Grahame et al. 1981); 5) An increasing number of discrete disorders of connective tissue such as the Ehlers-Danlos (EDS) and Marfan syndromes have been recognised. There is considerable overlap of variants of some of these conditions with familial undifferentiated joint hypermobility (Beighton et al. 1969; Walker et al. 1969)

The Ehlers—Danlos syndrome (EDS) is an inherited disorder of connective tissue which is characterised by the clinical triad of articular hypermobility, dermal extensibility and cutaneous scarring. The manifestations are very variable although usually fairly consistent within any kindred, and it has become increasingly evident that EDS is very heterogeneous.

In addition to the Ehlers—Danlos syndrome (EDS) (Chap. 9) and the familial undifferentiated hypermobility syndromes (Chap. 10), joint laxity is present in a number of inherited disorders. In some it is a major feature, while in others the hypermobility is overshadowed by other syndromic components.

Hypermobile patients can be spared much unnecessary suffering by the establishment of the correct diagnosis. As indicated in Chap. 6, hypermobility is one of the great mimics in rheumatology. Many hapless individuals are misdiagnosed as suffering from rheumatoid arthritis (both adult and juvenile). Needlessly they are forced to suffer the anguish of living with that diagnosis and are exposed to the dangers of the slow-acting anti-rheumatoid drugs and other potentially hazardous treatments. Others, in the absence of observed physical signs to explain their symptoms (joint hypermobility is often overlooked), are labelled as neurotic. They either accept this and become resigned to a life of misery and disability, or reject it and go from one specialist to another in their quest for relief. Not surprisingly many seek help from practitioners of alternative medicine. It is self-evident that reassuring the patient that he or she has neither a potentially crippling disease nor, for that matter, a psychological one can have a profoundly beneficial effect on morale!

In pathology there has always been an urge to find a “unifying concept” and a “basic defect” in a group of conditions with clinical similarities. So it has been with joint hypermobility. However this is not always a legitimate goal, and, except at a very superficial level, does not help us to understand the molecular basis of abnormal joint laxity. The reason for this lies in the diverse aetiologies of joint hypermobility, which span the inherited and the acquired, with both qualitative and quantitative differences in joint tissues. “But surely it’s a collagen defect?” is a common and understandable response — indeed one which has influenced the direction of research into the molecular basis of hypermobility. Why should this be so? Firstly, common sense tells us that the collagenous components of the joint connective tissues dictate the mechanical limitations of movements; after all, we are all aware of the physical attributes of tendons, ligaments and joint capsules — notably their tensile strength and high elastic modulus (resistance to deformation). Secondly, joint laxity can undoubtedly occur when these tissues are physically weakened — either surgically or by the erosion accompanying, for instance, rheumatoid arthritis. Thirdly, some genetic defects of collagen biosynthesis have been identified and associated with joint hypermobility — notably variants of the Ehlers—Danlos syndrome (EDS) and osteogenesis imperfecta (see Chap. 10). Fourthly, pharmacological interference with collagen biosynthesis, for instance with d-penicillamine, can increase joint laxity.