Cattalini et al. Pediatric Rheumatology (2015) 13:40 DOI 10.1186/s12969-015-0039-3 REVIEW Open Access When flexibility is not necessarily a virtue: a review of hypermobility syndromes and chronic or recurrent musculoskeletal pain in children Marco Cattalini1, Raju Khubchandani2 and Rolando Cimaz3* Abstract Chronic or recurrent musculoskeletal pain is a common complaint in children. Among the most common causes for this problem are different conditions associated with hypermobility. Pediatricians and allied professionals should be well aware of the characteristics of the different syndromes associated with hypermobility and facilitate early recognition and appropriate management. In this review we provide information on Benign Joint Hypermobility Syndrome, Ehlers-Danlos Syndrome, Marfan Syndrome, Loeys-Dietz syndrome and Stickler syndrome, and discuss their characteristics and clinical management. Keywords: Hyperlaxity, Musculoskeletal pain, Ehlers-Danlos, Marfan, Loeys-Dietz, Stickler Introduction Review Chronic or recurrent musculoskeletal pain is a common Benign joint hypermobility syndrome (BJHS) complaint in children, affecting between 10 % and 20 % Children with hypermobile joints by definition display a of children. It is one of the more frequent reasons for range of movement that is considered excessive, taking seeking a primary care physician’sevaluationandpos- into consideration the age, gender and ethnic background sible rheumatology referral [1, 2]. A wide variety of of the individual. It is estimated that at least 10–15 % of non-inflammatory conditions may cause musculoskel- normal children have hypermobile joints and the term etal pain in the pediatric age, and the most common joint hypermobility syndrome (JHS) is reserved to the causes seen by paediatric rheumatologists include cases of joint hypermobility associated with symptoms conditions associated with hypermobility. Hypermobil- with no other causes found for them [4–6]. JHS can be as- ity may have a significant impact on quality of life of sociated with hereditary connective tissue disorders, and affected children and their parents, even in the milder the term “Benign” is used in contrast to more serious and forms [3]. All physicians and allied professionals that potentially complicated or life-threatening musculoskeletal may be involved in the care of children with musculoskel- syndromessuchassomeformsofEhlers-Danlossyn- etal complaints should therefore be well trained to drome (EDS), Marfan syndrome, and Loeys-Dietz recognize hypermobility and to run the differential diag- syndrome. The prevalence of JHS is not known with nosis between the various clinical entities associated with precision, given the lack of studies of large cohorts. it. A critical approach to a child with hypermobility is cru- Sperotto et al., conducted a cross sectional study in a co- cial to correctly identify the underlying cause and avoid hort of healthy schoolchildren, aged 8–13 years from the time/money- consuming investigations. province of Padua, Italy, and found that BJHS occurred in In this paper we review different etiologies of muscu- the 13,2 % of the 289 children evaluated [7]. loskeletal pain associated with hypermobility, including Even if BJHS is very common, this condition is largely some genetic disorders, and discuss the clinical approach under-recognized by primary care physicians and often in these children. poorly managed. Symptoms frequently start in childhood and continue into adult life. The pathophysiology of be- * Correspondence: [email protected] nign joint hypermobility is unclear. Hypermobility is 3Anna Meyer Children’s Hospital and University of Florence, Florence, Italy more common in childhood and adolescence, in females, Full list of author information is available at the end of the article © 2015 Cattalini et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Cattalini et al. Pediatric Rheumatology (2015) 13:40 Page 2 of 9 and in some ethnicities, and it tends to lessen during of BJHS in children with JFM. Furthermore, children adulthood. Still, polyarticular hypermobility may be who have both JFM and BJHS may exhibit lower tender- present in up to 30 % of males and 40 % of females points thresholds and a greater number of tender-points during early adulthood [8]. For the majority of individ- compared to children with JFM but no benign joint hy- uals joint hypermobility may be of no consequence, permobility [15]. and what brings a proportion of subjects to develop The “Beighton score” (derived from the original one BJHS is not fully understood. BJHS seems to be trans- by Carter and Wilkinson) is commonly used to diagnose mitted by an autosomal pattern, and first-degree rela- hypermobility. Hypermobility is present if 4 out of 9 tives with the disorders can be identified in many points are scored. When this score is applied to normal cases. Variable penetrance is generally observed [9]. children, a large proportion of the population is hyper- With the exception of a minority of patients, who mobile (Table 1, Figs. 1, 2 and 3). This reflects the fact show a deficiency of tenascin X, no abnormality in col- that, as already discussed, connective tissue structures lagen or related proteins has been identified as a cause may be looser and joints hypermobile in childhood, es- for BJHS [10]. Joint pain is thought to be caused by ex- pecially compared to adults. For these reasons it may be cessive movement, increasing stress on joint surfaces, better to consider a Beighton score of 5 or more positive ligaments and adjacent structures. Other factors may [16]. The Beighton score has been incorporated into a contribute to the development of the syndrome, such more comprehensive set of criteria called the Brighton as poor proprioception, autonomic dysfunctions and Criteria (Table 2), which take into account the possible fatigue secondary to poor sleep [11]. multisystemic nature of this condition. Although these The predominant presenting complaint is pain, which criteria have not been formally validated in a pediatric may be widespread and debilitating. The pain typically population, they have been used in some studies on chil- starts during or after activity. The most common dren with hypermobility [17–19]. affected sites are the lower limbs after walking (for ex- The management of individuals with BJHS can be very ample walking to and from school). Children usually re- challenging and there are no evidence-based manage- port excess fatigue, handwriting difficulties or ‘clicking ment strategies currently available. Acute pain episodes or cracking’ joints. Occasionally episodes of joint swell- are commonly managed using taping, bracing or splint- ing lasting hours to days, joint dislocations, or more ing or with non-steroidal anti-inflammatory drugs as commonly subluxations with spontaneous reduction needed. However reassurance and a multi-disciplinary are reported. Back-pain is also a common complaint training program are the mainstays of long term man- because the lumbar spine is one of the most mobile agement. Physical therapy is of the outmost importance, sections of the vertebral column and the excessive and encouraging an active lifestyle may improve function movements may lead to pain in hypermobile subjects. and enhance quality of life [20]. As general principles, Heavy school bags are often an aggravating feature. strengthening exercises focused on muscles around Chronic pain results in a reduced exercise tolerance hypermobile joints may help to enhance joint support and can negatively impact patients’ life. throughout movement and reduce pain; closed chain ex- A significant proportion of subjects progressively quit ercises may enhance proprioceptive feedback and sports and other physical activities. In addition, pain optimize muscle action. Proprioception may be im- amplification is a common feature in these cases [12]. proved also by coordination and balance exercises. Phys- BJHS has been considered to cause only musculoskeletal ical therapy should also encompass a generalized symptoms for many years, but there is now mounting exercise programme, addressing cardio-respiratory, mus- evidence that many other extra-skeletal manifestations culoskeletal and neurological aspects of movement with may occur. This symptoms arise usually after the third the aim to reduce deconditioning [20]. As already decade of life, but have been described in adolescents, and may be due to connective tissue abnormalities, link- Table 1 Beighton scoring system for joint hypermobility ing BJHS and other hereditary disorders of connective (adapted from Junge et al. [16]) tissues, namely Ehlers-Danlos syndrome type III. These Scoring 1 point each side include functional and anatomic gastrointestinal tract 1. Passive dorsiflexion of the 5th metacarpophalangeal joint to >90° abnormalities (constipation, bloating, diarrhea, hiatal 2. Passive apposition of thumb to the flexor aspect of forearm hernias), autonomic dysfunctions (postural tachycardia