Academic Unit of Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK
Correspondence to: H. A. Bird, Academic Unit of Musculoskeletal Medicine, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK. E-mail: howard.bird{at}leedsth.nhs.uk
The late Dr Barbara Ansell frequently stated that hypermobility is tricky in children. That joint hypermobility should more frequently occur in children than in adults is undoubted. This is normally attributed to the stabilization of joint collagen that occurs as a result of increased cross-linking between adjacent molecules as disulphide bridges form with ageing. However, this is not the whole picture because most authorities agree that joint laxity increases up to a maximum at the time of adolescence, only decreasing thereafter. Presumably the stretching effect of growth on collagen predominates over decline, additional spurts of hypermobility apparently accompanying each of the growth spurts in either sex and the onset of menstruation in females. The first seminal description of hypermobility as a syndrome and frequently recognized as a cause of symptoms, often severe, came from Dr Ansell and her colleagues in 1967 [1]. It has also long been recognized that symptoms arising from hypermobile joints in children can mimic pauciarticular inflammatory polyarthritis [2], a situation also found in adults [3].
Compartmentalization within medicine can be a mixed blessing. Although the advent of paediatric rheumatology, now recognized increasingly as a subspeciality, provides obvious benefits to many children and their parents, the case for a clear separation between the management of children and adults is least strong in the field of inherited abnormalities, particularly those of connective tissue. Often the review in the same clinic of three generations within a single affected family may be necessary to clearly delineate and quantify the clinical phenotype. This, in turn, paves the way for molecular genetics.
Research into hypermobility is also changing, in large part influenced by advances in molecular medicine. Traditionally the syndrome was notified, quantified and then ignored. Early scoring systems, notably those from Carter and Wilkinson [4] and the 1973 modification of this by Beighton et al. [5], concentrate on an appraisal of the joint laxity, reducing it to a single figure. Although this was of value in epidemiological studies (and still is), this approach ignored the fact that collagen is not only ubiquitous throughout the body but exists in many different forms at different sites and that, in turn, joint hypermobility might simply be a phenotypic marker for problems likely to occur elsewhere. The Brighton 1998 criteria for the diagnosis of the syndrome [6] attempted to address this, retaining the earlier quantification of joint laxity but adding additional clinical features increasingly recognized with joint hypermobility. The ARC information pamphlet attempts to define four possible contributing factors to the observed phenotype comprising: collagen structure, the shape of the bony articulating surface, neuromuscular tone and joint proprioception [7]. An excellent, more comprehensive pamphlet from The Hypermobility Syndrome Association (HMSA) [8] lists the majority of the many clinical symptoms that can accompany hypermobility in children with practical advice on how to address them. The booklet is available upon request by post from HMSA, P.O. Box 1122, Nailsea, Bristol BS48 2YZ, UK. A companion booklet aimed at adults is in preparation.
Against this background, descriptive research on children delineating joint hypermobility with all its features is to be welcomed in a journal predominantly devoted to adult rheumatology since these subjects, whose symptoms will not be restricted to childhood, will ultimately pass into the hands of rheumatologists and orthopaedic surgeons treating adults. This issue of Rheumatology contains such a paper from Adib and colleagues at Great Ormond Street [9]. The paper describes 125 children (61 males and 64 females) who were studied on the basis that in each an experienced paediatric rheumatologist had considered the individuals both to have a hypermobility syndrome and to have suffered adverse symptoms as a result of this. All were aged less than 18 yr. Eyebrows might be raised at the method of selection, which would not provide true epidemiological evidence of prevalence and a hospital of tertiary referral is inevitably likely to see a highly selected group of patients. That patients were also derived from two sources, one a clinic specifically dedicated to paediatric hypermobility and the other a cull of hospital records, both out-patients and in-patients, in search of the diagnosis, also probably slants the study to the most extreme examples of the condition. Nevertheless, such a study has not previously been performed in such detail and the findings make instructive reading.
Although three-quarters of referrals came from paediatricians and GPs, the condition was generally unrecognized, the joint symptoms not normally attributed to hypermobility alone. Twenty per cent of individuals gave a history of recurrent joint sprain and there was actual subluxation or dislocation in 10%. In 63% there was joint hyperlaxity in a first-degree relative. The lax sphincters typically associated with this condition probably account for the frequency of urinary tract infection and urinary tract dysfunction in this group of individuals. Indeed, if the proportion of females in the series had been higher (the comparable frequency in males and females is unusual and not quite in keeping with other literature), this might have been more pronounced.
That the mean age of first walking was delayed and that 48% were considered clumsy, 36% with poor coordination in early childhood, raises several interesting points. This is sometimes the only obvious clinical symptom in the more seriously affected and emphasizes the need to exclude a primary inherited abnormality of muscle. Impaired proprioception is increasingly associated with joint hypermobility, not only at the knee [10] but also at the hand [11]. Therefore the possibility that proprioception alone might be the cause of the delayed walking arises; it is also conceivable that impaired proprioception in the fingers might handicap writing skills. It has recently been shown [12] that enhancement of proprioception in patients ameliorates symptoms; perhaps exercises to enhance proprioception might also improve function. It would also be interesting to determine whether, on the basis of subsequent follow-up (or study of adults from the same family), it was this group who ultimately were particularly susceptible to premature osteoarthritis.
The paper also only partially dissects the influence of race on phenotype. Earlier work from South Africa [5] has convincingly shown that even where different ethnic groups live in the same climate and circumstances, there is wide divergence in the joint laxity observed. The Europeans are most stiff; the Bantu tribes of intermediate joint laxity and those originally from the Indian subcontinent of most marked joint laxity. In the global village that is London only 99 out of 125 were classified as Caucasian, the remainder almost constituting a small United Nations. A small proportion was of mixed parentage. In Caucasians the genes for laxity are thought to have greater penetration in females (though this may in part be hormonal). Study of the mixed group might clarify whether this held true in those of more diverse ethnic origin. Worldwide, small pockets of extreme hypermobility have existed since antiquity, e.g. Hippocrates description of the Scythians who had so much hyperextensibility of the elbows that they proved inefficient as bowmen. Recent interest has concentrated on northern Iraq [13] and the Yoruba of Nigeria [14]. This might also skew the results in an urban population and it would be of interest to know if the joint laxity was maintained in a new environment.
The study is devoted to the benign joint hypermobility syndrome, deliberately excluding more serious specific inherited abnormalities of connective tissue such as EhlersDanlos syndrome, Marfan's syndrome, osteogenesis imperfecta and (presumably) skeletal dysplasias. There also seem to be no representatives with Stickler's syndrome, an abnormality of type II collagen causing ocular and musculoskeletal abnormalities, which is inherited as an autosomal dominant condition and estimated to occur in 1 in 10 000 live births [15]. In spite of this, the authors find and comment on considerable overlap between benign hypermobility and mild variants of these other conditions. A separate literature already attests to some mosaicism between these various discrete conditions. The prevalence of osteogenesis imperfecta is normally given as 1 in 20 000 [16]; the prevalence of type I EhlersDanlos syndrome as 1 in 20 000; and that of type IV EhlersDanlos syndrome (the vascular variant) as 1 in 100 000 [17]. If these prevalence rates are accepted, such conditions are unlikely to have contributed significantly to this particular series, but the possibility remains that there may be several more mild variants of these rarer conditions, all with varying degrees of penetrance within the same family.
Perhaps, sensibly, the study therefore sidesteps the question most frequently asked by the accompanying parents, which concern the chances of other children being affected if they enlarge their family. It also makes no mention of a further problem associated with this group, which is the propensity to easy bruising and even fracture on minimal trauma, which sometimes leads to an erroneous diagnosis of child abuse when the injuries first present in the casualty department. This information is perhaps more likely to emerge from a study of the local casualty records and may be less apparent in a centre of tertiary referral.
The field remains complex and interesting, rejuvenated by the recent dramatic advances in molecular genetics. These have recently been summarized eloquently by Pope [18], the number of recognizable genetic abnormalities expanding by the month if not the day. In general, clinical documentation of the phenotype resulting from these molecular abnormalities has been a limiting factor, so descriptive studies of this sort, which behove us to collect more detailed clinical information not just in affected children but in their affected parents and grandparents thus crossing the rheumatological age divide, become all the more important.
The author has declared no conflicts of interest.
References
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