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doi:10.1111/jpc.12731
REVIEW ARTICLE
Joint hypermobility syndrome: A review for clinicians Verity Pacey,1,6 Louise Tofts,2 Alison Wesley,3 Felicity Collins4 and Davinder Singh-Grewal5 Departments of 1Physiotherapy, 2Rehabilitation, 3Occupational Therapy, 4Clinical Genetics and 5Rheumatology, The Children’s Hospital at Westmead and Department of 6Health Professions, Macquarie University, Sydney, New South Wales, Australia
Abstract: The term ‘joint hypermobility’ describes synovial joints that move beyond a normal range of motion. ‘Joint hypermobilty syndrome’ may also be associated with significant symptoms and impaired quality of life. The purpose of this review is to help the generalist to recognise the condition, exclude significant alternative diagnoses and understand the multidisciplinary approach to management. Key words:
genetics; hypermobility; pain; rehabilitation.
Generalised hypermobility is defined using the Beighton score1 (Fig. 1). A score of ≥4/9 defines hypermobility, although the age of the child must be considered. It is more common in females,2 especially in Asian and African populations, with up to 40% of females in some races affected.3–5 Hypermobile individuals are often entirely asymptomatic and utilise their increased flexibility to advantage in sports; however, around 50% of these individuals report hypermobility-related pain.6 Many significant heritable disorders of connective tissue (HDCTs) are associated with hypermobility, but the majority of patients with hypermobility have no identifiable HDCTs. Hypermobility associated with symptoms, as defined by the Brighton criteria (Table 1), is termed joint hypermobility syndrome (JHS). Unfortunately, the Brighton criteria are often confused with the Beighton score, which is used only to define hypermobility as such. Though the Brighton criteria are not validated in children, they are useful in the diagnosis of childhood JHS.7,8 Joint pain is the commonest symptom of JHS, often associated with dislocations, subluxations and sprains. Cognitive, Key Points 1 Joint hypermobility is relatively common, but some patients experience significant symptoms as a result of this condition, many of which manifest outside the musculoskeletal system. 2 A number of heritable disorders of connective tissue are associated with joint hypermobility and should be considered when assessing patients with hypermobility, as they can have wider implications for the patient. 3 Effective management requires engagement of a multidisciplinary team in the most severely affected patients. Correspondence: Dr Davinder Singh-Grewal, Department of Paediatric Rheumatology, The Children’s Hospital at Westmead, Sydney, NSW 2145, Australia. Fax: 9845 3432; email: [email protected] Conflict of interest: None. Accepted for publication 22 July 2014.
neurological and visceral manifestations are frequent and may be more disabling than musculoskeletal symptoms.9 Fatigue and generalised pain9,10 are common issues, with hyperaesthesia resulting from increased nociception of overstretched tissues a likely explanation. Pain frequently results in inactivity, with resultant deconditioning exacerbating symptoms. Gastrointestinal manifestations such as chronic constipation, gastro-esophageal reflux, chronic abdominal pain and irritable bowel syndrome are commonly reported in JHS, as are symptoms of syncope, dizziness and orthostatic hypotension.11,12 These features together are often cited as evidence for autonomic dysfunction in JHS. Anxiety has also been linked to JHS in adults and may exacerbate autonomic and chronic pain manifestations.13
Joint Hypermobility and HDCTs The term ‘joint hypermobility syndrome’ is used to refer to a particular combination of symptoms and signs.14 In the absence of a diagnostic test, careful clinical examination and exclusion of severe HDCTs is required (Fig. 2). Down, Klinefelter and fragile X syndromes, as well as rare skeletal dysplasias (including pseudoachondroplasia) associated with ligamentous laxity and joint hypermobility, should be considered, especially where there is disproportionately short stature. Children with rare muscular dystrophies such as Ullrich dystrophy (COL6A2) may present with a mix of distal hypermobility, proximal weakness and contractures. Muscle weakness may be mistaken for joint hypermobility without thorough neurological examination. Individuals with Marfan syndrome (fibrillin 1; FBN1 gene) may have ligamentous laxity and reduced muscle mass, with limitation of elbow joint extension. It is important to exclude the vascular form of Ehlers–Danlos syndrome (EDS) (type IV; COL3A1) because of the propensity for arterial and organ rupture. Features such as skin translucency and excessive bruising, along with family history of sudden vascular death in early adulthood,16 are clues to a possible diagnosis of a vascular form of EDS. JHS may be part of the HDCT spectrum where the degree of skin and vascular involvement is
Journal of Paediatrics and Child Health (2014) © 2014 The Authors Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
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(a)
(b)
(d)
(e)
(c)
Fig. 1 Beighton score. Points are awarded for the following: (a) fifth-finger metacarpophalangeal joint extension >90° (one point for each side); (b) ability to touch thumb to forearm (one point for each side); (c) elbow extension >10° (one point for each side); (d) knee extension >10° (one point for each side); (e) ability to touch palms flat to floor with knees straight (one point). Scores ≥4 (out of 9) indicate generalised joint hypermobility.
less than in the other forms of EDS (Table 2), and a diagnosis of EDS hypermobility type (EDS-HT, previously called EDS type III) is often considered when hypermobility and mild skin involvement are present.14,19 The clinical features of JHS and EDS-HT are indistinguishable.20 When the Brighton criteria for JHS were defined, it was acknowledged that individuals with Marfan syndrome, osteogenesis imperfecta and other more severe forms of EDS may have symptoms of JHS, but these conditions were ‘excluded’.19 Since the Brighton conference, several new disorders associated with Marfan-like features and newer forms of EDS have been identified. Importantly, Loeys–Dietz syndrome (LDS) has been identified as an HDCT with specific facial dysmorphism (hypertelorism, bifid uvula, cleft palate), Marfanoid habitus, and generalised arterial tortuosity and risk of arterial rupture.21 As knowledge of this condition has increased, the LDS spectrum has broadened to include individ2
uals of normal stature and minimal facial dysmorphism with persistent arterial tortuosity risk. Joint hypermobility is very common in LDS, particularly in childhood.22 At least four different genes (TGFBR1, TGFBR2, TGFB2, SMAD3) have now been determined to cause LDS,23 emphasising the role of noncollagen extracellular matrix proteins and intracellular factors in causing HDCT associated with systemic symptoms. A few patients with JHS have been reported with deficiency of an extracellular glycoprotein called tenascin X due to loss of function of the TNXB gene, usually in conjunction with features of congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CYP21B gene deletion).17 Given that JHS may occur in association with several welldefined HDCTs that are difficult to distinguish clinically from EDS-HT, it is important to consider these diagnoses (Fig. 2) and refer, when appropriate, for further investigations such as echocardiographic and ophthalmological examination and
Journal of Paediatrics and Child Health (2014) © 2014 The Authors Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
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Table 1
Brighton criteria for joint hypermobility syndrome
Major criteria • Beighton score of ≥4 • Arthralgia for longer than 3 months in four or more joints Minor criteria • Beighton score of 1, 2 or 3 • Arthralgia (>3 months) in one to three joints, back pain (>3 months), or spondylosis/spondylolysis/spondylolisthesis • Dislocation or subluxation in more than one joint, or in one joint on more than one occasion • Three or more soft tissue lesions (e.g. epicondylitis, tenosynovitis, bursitis) • Marfanoid habitus (tall, slim, span greater than height (>1.03 ratio), upper segment less than lower segment (16 weeks) may make chronic pain worse, as well as causing dependence.33 Some patients with chronic pain may benefit from pharmacological therapies beyond simple analgesia to modify pain perception, such as selective serotonin re-uptake inhibitors, tricyclic antidepressants, and anti-epileptics such as gabapentin, though these drugs should be used cautiously and not on a long-term basis. Pharmacological therapies do not provide longlasting symptom control in JHS and should not be relied on in isolation without a physical and psychological treatment plan.
Joint and soft tissue injury Joint instability and injury are common complaints in children with JHS, with the knee the most affected joint.9 Reduced joint proprioception, reduced muscle power,34 altered movement strategies,35 poor balance26 and reduced physical fitness,36 along
Journal of Paediatrics and Child Health (2014) © 2014 The Authors Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
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A ru r teri pt al ur e
Cleft palate Bifid uvula Pectus Scoliosis BAV / ASD / PDS Allergy MVP Bowel Dysautonomia TEV Pes planus dislocations Osteopenia Blue CDH EDS-HT / sclerae
Uterine rupture Progeria
Bruising
JHS
Atrophic scars
Hearing loss
OI Fractures
Skin fragility
Fig. 2 Overlapping features in heritable disorders of connective tissue presenting with joint hypermobility. Adapted from Grahame.15 ASD, atrial septal defect; BAV, bicuspid aortic valve; CDH, congenital dysplasia of the hips; EDS, Ehlers–Danlos syndrome; EDS-HT, Ehlers–Danlos syndrome hypermobility type; JHS, joint hypermobility syndrome; MVP, mitral valve prolapse; OI, osteogenesis imperfecta; PDA, persistent ductus arteriosus; TEV, talipes equinovarus.
with underlying connective tissue fragility present in JHS, may all contribute to the increased risk of injury. Injury management should follow the usual course, with emphasis placed on addressing contributing factors that are amenable to change. Recovery from injury may take longer in individuals with JHS,37 particularly the recovery of muscular strength and endurance.27 Injuries should be treated promptly by clinicians with expertise in managing hypermobility and sports injuries to avoid the development of chronic symptoms.
Physical activity Participation in everyday activities is significantly reduced in children with JHS.26 Children with JHS report difficulties participating in school physical education classes,9 and reduced participation in sporting activities continues into adulthood.38 The relationship between hypermobility and gross motor skill proficiency is unclear in the general population, but hypermobility is disadvantageous in those children with developmental co-ordination disorder.39 Generalised joint hypermobilty may be advantageous in activities such as ballet or gymnastics. However, an increased incidence of pain and injury in individuals with JHS may prevent the child from progressing to higher levels within these fields.40 A thorough assessment of the child’s hypermobility and active joint stability will assist clinicians in guiding families in choosing physical activities that children can undertake with minimal pain and injury while still reaping the social and health benefits. Care should be taken with contact sports, particularly if the child is hypermobile in the cervical spine (extension range 90° 4
or more). Knee joint injuries are almost five times more likely to occur in hypermobile participants of contact sports,41 and finger injuries are common in ball sports such as netball.42 Individual non-contact activities such as swimming or Pilates are often recommended27; however, many children prefer team sports.
Hand function and handwriting Impaired hand function is a common disabling symptom in JHS,9,38 with handwriting difficulty reported in up to 40% of patients. Instability may be present at the interphalangeal, metacarpophalangeal and carpometacarpal joints of the thumb and the distal and proximal interphalangeal joints of the index and middle fingers. The wrist is often implicated. To compensate, students with JHS frequently adopt a palmar grasp, increasing the skin surface area on the writing implement with the index and middle fingers overlapped by the thumb. The resultant firm and immobile grasp restricts movement, as the muscles are engaged in supporting the joints, placing strain on the hand, the forearm and often the upper arm. Examples of these grips are seen in Figure 3.43 These static grasps contribute to muscle fatigue, pain, and decreased handwriting legibility, speed and endurance.9,44 Students with JHS may have difficulty producing written output required to meet classroom demands. Long-term handwriting difficulties may have significant negative implications for academic performance, learning and self-esteem.45 Specific techniques to assist with handwriting include using assistive equipment such as back cushions, footstools, slope boards and pen grips to ensure an ergonomic posture when writing. Splints and taping are used to provide external stability
Journal of Paediatrics and Child Health (2014) © 2014 The Authors Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
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Table 2 Ehlers–Danlos syndrome classification and summary of major types17,18 Villefranche classification
Inheritance
Body parts involved
Features
Genes
Classical (I, II)
Autosomal dominant
Skin Joints
COL5A1, COL5A2 (>50%); COL1A1
Hypermobility (III)
Autosomal dominant
Vascular (IV)
Autosomal dominant
Joints Skin Gastrointestinal tract Central nervous system Vascular system Viscera Joints Skin
Fragility Hyperextensibility Atrophic scars Easy bruising Hypermobility Sprains, dislocations Generalised hypermobility Pain/fatigue Soft, doughy skin
COL3A1
Kyphoscoliotic (VIA)
Autosomal recessive
Joints Eyes Skin
Arthrochalasic (VIIA, VIIB)
Autosomal dominant
Joints Skin
Dermatosparaxis (VIIC)
Autosomal recessive
Skin
Arterial rupture Uterine rupture Bowel perforation Hypermobility, especially distal Acrogeria Excess bruising Thin, translucent skin Congenital, progressive Scoliosis Hypermobility Microcornea Scleral fragility – globe rupture Fragility, bruising Congenital hip dislocation Recurrent joint dislocation Hypermobility Hyperextensibility, fragility Severe fragility Sagging skin Premature rupture of membranes Herniae
Other rare forms Musculocontractural type (EDS VIB)
Autosomal recessive
Brittle cornea syndrome (EDS VIB)
Autosomal recessive
OCULAR Skin joints
Spondylocheirodysplastic
Autosomal recessive
Skin Joints ocular
Arthrogryposis Joint dislocation Joint laxity kyphoscoliosis hypotonia; skin laxity hydronephrosis Myopia, keratoconus, Brittle cornea Joint laxity Scoliosis Skin fragility Short stature; Small hands, finger contractures; Skin hyperelasticity; Joint hypermobility
Journal of Paediatrics and Child Health (2014) © 2014 The Authors Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
TNXB (10%), other unknown genes
PLOD1
COL1A1, COL1A2
ADAMTS2
CHST14; DSE
ZNF469; PRDM5
SLC39A13
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(a) Table 3 Baseline investigations and referrals to consider in patients with hypermobility24 • • • • • • •
Chromosome microarray Fragile X gene test, especially in developmental delay in males Urine metabolic screen Skeletal survey (if patient is of short stature) Echocardiogram Ophthalmological examination Non-invasive vascular imaging (magnetic resonance imaging/angiogram) • Referral for genetic testing to exclude identifiable heritable disorders of connective tissue
to distal joints, allow more fluid movement, and prevent or delay the onset of pain and fatigue. Despite a lack of published evidence, the use of splinting has been observed to reduce pain and improve endurance. In relation to curriculum access, frequent rest breaks are required, particularly during writing-intensive subjects and examination procedures. For students who experience pain within minutes of writing, alternative strategies such as accessing other students’ notes or using technology such as tablet devices or computers are required. Liaison with the school is important to ensure strategies can be implemented throughout the day. Classrooms may be timetabled close together or on the ground floor to limit the amount of walking between classes. Students are advised to use lockers and to have a second set of textbooks to avoid carrying heavy bags.
(b)
Fatigue Fatigue is a disabling symptom for the majority of children with JHS.10 Children with JHS often do not report fatigue unless questioned or objectively assessed, possibly because of difficulties describing it, or because they have lived with it for some time and do not realise what is normal. The cause of fatigue in this population remains unknown, and it is likely to be multifactorial in nature. Screening children with disabling fatigue for other conditions is often warranted. A diagnosis of chronic fatigue syndrome (CFS) is excluded by the presence of underlying JHS, but the standard multidisciplinary approach to CFS is usually beneficial.46 Poor sleep,47 muscle weakness48 and dysautonomia49 have all been shown to be associated with worse fatigue in JHS. Physiotherapy-based graded reconditioning programmes seem to be helpful, and anecdotally, aquatic physiotherapy seems efficacious for children with fatigue that interferes with their day-to-day activities. Cognitive–behavioural therapy including self-management and pacing advice is widely recommended, and involvement of a psychologist and the child’s school is important in sustaining improvement. Sleep dysfunction is also frequently observed in children with JHS9 and should be addressed, as it may potentiate chronic pain and fatigue.
Psychological interventions Patients with JHS are known to have fluctuating symptom patterns that can be unpredictable and disruptive to their 6
Fig. 3 Variations in pencil grip seen in children with joint hypermobility. (a) Lateral quadrupod pencil grasp. The thumb variably overlaps the index, third and fourth fingers, keeping the pencil in the palm of the hand. This is a firm and immobile grasp that prevents distal control of the fingers and can result in strain of the wrist and hand. Writing speed, endurance and legibility are affected by this type of grasp. (b) Lateral tripod pencil grasp. The thumb overlaps the index and middle finger, keeping the pencil in the palm of the hand. This is a static grasp that can cause muscle fatigue and pain with prolonged writing, resulting in impaired speed and legibility.
general functioning. ‘Boom and bust’ cycles are often established, where periods of relative symptom control can result in excessive activity, which can result in worsening symptoms and periods of inactivity, which in turn worsen symptoms. Patients, their families and their schools need to be educated about instituting a paced and graded activity programme that establishes a pattern of essential activities, including school and household tasks, that children need to be able to undertake before additional activities such as sports and recreation are added in a stepwise fashion. Psychological intervention to explore stressors and develop coping strategies for fatigue, chronic pain and anxiety is also essential in some patients.
Journal of Paediatrics and Child Health (2014) © 2014 The Authors Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
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Summary Joint hypermobility is a relatively common condition. It is occasionally associated with a significant underlying HDCT, which may have other important organ involvements. These should be actively excluded by physicians seeing these patients. Up to a half of hypermobile patients will have significant symptoms justifying a diagnosis of JHS. A combination of physical and psychological therapies is usually successful in controlling these symptoms and limiting their impact on a young person’s life. Attention to education and empowerment of the patient and family are essential as part of the development of effective self-management strategies. To ensure accurate diagnosis and appropriate management, clinicians must consider the possibility of JHS when assessing patients whose primary symptoms are musculoskeletal but who also present extra-articular manifestations such as fatigue, generalised pain, gastrointestinal dysfunction, postural hypotension or dizziness, and skin fragility.
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15 Grahame R. Heritable disorders of connective tissue. Baillieres Best Pract. Res. Clin. Rheumatol. 2000; 14: 345–61. 16 Oderich GS, Panneton JM, Bower TC et al. The spectrum, management and clinical outcome of Ehlers–Danlos syndrome type IV: a 30-year experience. J. Vasc. Surg. 2005; 42: 98–106. 17 Bristow J, Carey W, Egging D, Schalkwijk J. Tenascin-X, collagen, elastin, and the Ehlers–Danlos syndrome. Am. J. Med. Genet. C. Semin. Med. Genet. 2005; 139C: 24–30. 18 Keer R, Simmonds J. Joint protection and physical rehabilitation of the adult with hypermobility syndrome. Curr. Opin. Rheumatol. 2011; 23: 131–6. 19 Grahame R, Bird HA, Child A. The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS). J. Rheumatol. 2000; 27: 1777–9. 20 De Paepe A, Malfait F. The Ehlers–Danlos syndrome, a disorder with many faces. Clin. Genet. 2012; 82: 1–11. 21 Loeys BL, Chen J, Neptune ER et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat. Genet. 2005; 37: 275–81. 22 Erkula G, Sponseller PD, Paulsen LC, Oswald GL, Loeys BL, Dietz HC. Musculoskeletal findings of Loeys–Dietz syndrome. J. Bone Joint Surg. Am. 2010; 92: 1876–83. 23 Van Laer L, Dietz H, Loeys B. Loeys–Dietz syndrome. Adv. Exp. Med. Biol. 2014; 802: 95–105. 24 Branson JA, Kozlowska K, Kaczynski KJ, Roesler TA. Managing chronic pain in a young adolescent girl with Ehlers–Danlos syndrome. Harv. Rev. Psychiatry 2011; 19: 259–70. 25 Tofts LJ, Elliott EJ, Munns C, Pacey V, Sillence DO. The differential diagnosis of children with joint hypermobility: a review of the literature. Pediatr. Rheumatol. Online J. 2009; 7: 1. 26 Schubert-Hjalmarsson E, Ohman A, Kyllerman M, Beckung E. Pain, balance, activity, and participation in children with hypermobility syndrome. Pediatr. Phys. Ther. 2012; 24: 339–44. 27 Simmonds JV, Keer RJ. Hypermobility and the hypermobility syndrome. Man. Ther. 2007; 12: 298–309. 28 Kemp S, Roberts I, Gamble C et al. A randomized comparative trial of generalized versus targeted physiotherapy in the management of childhood hypermobility. Rheumatology (Oxford) 2010; 49: 315–25. 29 Pacey V, Tofts L, Adams RD, Munns CF, Nicholson LL. Exercise in children with joint hypermobility syndrome and knee pain: a randomised controlled trial comparing exercise into hypermobile versus neutral knee extension. Pediatr. Rheumatol. Online J. 2013; 11: 30. 30 Birt L, Pfeil M, MacGregor A, Armon K, Poland F. Adherence to home physiotherapy treatment in children and young people with joint hypermobility: a qualitative report of family perspectives on acceptability and efficacy. Musculoskeletal Care 2013; 12: 56–61. 31 McCulloch R, Redmond A. The hypermobile foot. In: Hakim AJ, Keer R, Grahame R, eds. Hypermobility, Fibromyalgia and Chronic Pain. London: Elsevier, 2010; 255–67. 32 Tobias JH, Deere K, Palmer S, Clark EM, Clinch J. Hypermobility is a risk factor for musculoskeletal pain in adolescence: findings from a prospective cohort study. Arthritis Rheum. 2013; 65: 1107–15. 33 Crofford LJ. Adverse effects of chronic opioid therapy for chronic musculoskeletal pain. Nat. Rev. Rheumatol. 2010; 6: 191–7. 34 Fatoye F, Palmer S, Macmillan F, Rowe P, van der Linden M. Proprioception and muscle torque deficits in children with hypermobility syndrome. Rheumatology (Oxford) 2009; 48: 152–7. 35 Fatoye FA, Palmer S, van der Linden ML, Rowe PJ, Macmillan F. Gait kinematics and passive knee joint range of motion in children with hypermobility syndrome. Gait Posture 2011; 33: 447–51.
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36 Engelbert RHH, van Bergen M, Henneken T, Helders PJM, Takken T. Exercise tolerance in children and adolescents with musculoskeletal pain in joint hypermobility and joint hypomobility syndrome. Pediatrics 2006; 118: e690–6. 37 Briggs J, McCormack M, Hakim AJ, Grahame R. Injury and joint hypermobility syndrome in ballet dancers – a 5-year follow-up. Rheumatology (Oxford) 2009; 48: 1613–14. 38 Rombaut L, Malfait F, Cools A, De Paepe A, Calders P. Musculoskeletal complaints, physical activity and health-related quality of life among patients with the Ehlers–Danlos syndrome hypermobility type. Disabil. Rehabil. 2010; 32: 1339–45. 39 Jelsma LD, Geuze RH, Klerks MH, Niemeijer AS, Smits-Engelsman BC. The relationship between joint mobility and motor performance in children with and without the diagnosis of developmental coordination disorder. BMC Pediatr. 2013; 13: 35. 40 McCormack M, Briggs J, Hakim A, Grahame R. Joint laxity and the benign joint hypermobility syndrome in student and professional ballet dancers. J. Rheumatol. 2004; 31: 173–8. 41 Pacey V, Nicholson LL, Adams RD, Munn J, Munns CF. Generalized joint hypermobility and risk of lower limb joint injury during sport. Am. J. Sports Med. 2010; 38: 1487–97. 42 Smith R, Damodaran AK, Swaminathan S, Campbell R, Barnsley L. Hypermobility and sports injuries in junior netball players. Br. J. Sports Med. 2005; 39: 628–31. 43 Koziatek SM, Powell NJ. Pencil grips, legibility, and speed of fourth-graders’ writing in cursive. Am. J. Occup. Ther. 2003; 57: 284–8. 44 Kirby A, Davies R, Bryant A. Hypermobility syndrome and developmental coordination disorder: similarities and features. Int. J. Ther. Rehabil. 2005; 12: 431–7. 45 Wallen M, Bonney M, Lennox L. Interrater reliability of the handwriting speed test. Occup. Ther. J. Res. 1996; 17: 280–7. 46 National Institute for Health and Care Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. London: National Institute for Health and Care Excellence, 2007. NICE Clinical Guidelines, No. 53. 47 Voermans NC, Knoop H, van de Kamp N, Hamel BC, Bleijenberg G, van Engelen BG. Fatigue is a frequent and clinically relevant problem in Ehlers–Danlos syndrome. Semin. Arthritis Rheum. 2010; 40: 267–74. 48 Voermans NC, Knoop H, Bleijenberg G, van Engelen BG. Fatigue is associated with muscle weakness in Ehlers–Danlos syndrome: an explorative study. Physiotherapy 2011; 97: 170–4. 49 Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am. J. Med. 2003; 115: 33–40.
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Multiple Choice Questions 1. Joint hypermobility syndrome is a disorder affecting which of the following? a. The musculoskeletal system only b. The musculoskeletal system and the skin c. The musculoskeletal and cardiovascular systems d. The musculoskeletal and gastrointestinal systems e. Multiple organ systems Answer: e Joint hypermobility syndrome is a multisystem disorder with variable presentation across patients. Multiple system involvement may include the joints, the skin and the gastrointestinal, cardiovascular and autonomic nervous systems. 2. Children with joint pain caused by or related to hypermobility often describe which of the following? a. Pain worse with activity b. Pain worse in the morning c. Persistent joint swelling d. No improvement with rest e. Improvement with non-steroidal anti-inflammatory medications Answer: a Options b, c and e are all features of inflammatory joint disease and should be considered as differential diagnoses. Symptoms of joint pain in joint hypermobility syndrome usually improve with rest. 3. Important contributors to chronic fatigue in joint hypermobility syndrome include which of the following? a. Poor sleep, hypothyroidism, deconditioning b. Dysautonomia, anaemia, muscle weakness c. Poor sleep, deconditioning, depression d. Poor sleep, dysautonomia, muscle weakness e. Coeliac disease, poor sleep, deconditioning Answer: d The others are all direct causes of fatigue and not regularly associated with joint hypermobility syndrome.
Journal of Paediatrics and Child Health (2014) © 2014 The Authors Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
doi:10.1111/jpc.12731
REVIEW ARTICLE
Joint hypermobility syndrome: A review for clinicians Verity Pacey,1,6 Louise Tofts,2 Alison Wesley,3 Felicity Collins4 and Davinder Singh-Grewal5 Departments of 1Physiotherapy, 2Rehabilitation, 3Occupational Therapy, 4Clinical Genetics and 5Rheumatology, The Children’s Hospital at Westmead and Department of 6Health Professions, Macquarie University, Sydney, New South Wales, Australia
Abstract: The term ‘joint hypermobility’ describes synovial joints that move beyond a normal range of motion. ‘Joint hypermobilty syndrome’ may also be associated with significant symptoms and impaired quality of life. The purpose of this review is to help the generalist to recognise the condition, exclude significant alternative diagnoses and understand the multidisciplinary approach to management. Key words:
genetics; hypermobility; pain; rehabilitation.
Generalised hypermobility is defined using the Beighton score1 (Fig. 1). A score of ≥4/9 defines hypermobility, although the age of the child must be considered. It is more common in females,2 especially in Asian and African populations, with up to 40% of females in some races affected.3–5 Hypermobile individuals are often entirely asymptomatic and utilise their increased flexibility to advantage in sports; however, around 50% of these individuals report hypermobility-related pain.6 Many significant heritable disorders of connective tissue (HDCTs) are associated with hypermobility, but the majority of patients with hypermobility have no identifiable HDCTs. Hypermobility associated with symptoms, as defined by the Brighton criteria (Table 1), is termed joint hypermobility syndrome (JHS). Unfortunately, the Brighton criteria are often confused with the Beighton score, which is used only to define hypermobility as such. Though the Brighton criteria are not validated in children, they are useful in the diagnosis of childhood JHS.7,8 Joint pain is the commonest symptom of JHS, often associated with dislocations, subluxations and sprains. Cognitive, Key Points 1 Joint hypermobility is relatively common, but some patients experience significant symptoms as a result of this condition, many of which manifest outside the musculoskeletal system. 2 A number of heritable disorders of connective tissue are associated with joint hypermobility and should be considered when assessing patients with hypermobility, as they can have wider implications for the patient. 3 Effective management requires engagement of a multidisciplinary team in the most severely affected patients. Correspondence: Dr Davinder Singh-Grewal, Department of Paediatric Rheumatology, The Children’s Hospital at Westmead, Sydney, NSW 2145, Australia. Fax: 9845 3432; email: [email protected] Conflict of interest: None. Accepted for publication 22 July 2014.
neurological and visceral manifestations are frequent and may be more disabling than musculoskeletal symptoms.9 Fatigue and generalised pain9,10 are common issues, with hyperaesthesia resulting from increased nociception of overstretched tissues a likely explanation. Pain frequently results in inactivity, with resultant deconditioning exacerbating symptoms. Gastrointestinal manifestations such as chronic constipation, gastro-esophageal reflux, chronic abdominal pain and irritable bowel syndrome are commonly reported in JHS, as are symptoms of syncope, dizziness and orthostatic hypotension.11,12 These features together are often cited as evidence for autonomic dysfunction in JHS. Anxiety has also been linked to JHS in adults and may exacerbate autonomic and chronic pain manifestations.13
Joint Hypermobility and HDCTs The term ‘joint hypermobility syndrome’ is used to refer to a particular combination of symptoms and signs.14 In the absence of a diagnostic test, careful clinical examination and exclusion of severe HDCTs is required (Fig. 2). Down, Klinefelter and fragile X syndromes, as well as rare skeletal dysplasias (including pseudoachondroplasia) associated with ligamentous laxity and joint hypermobility, should be considered, especially where there is disproportionately short stature. Children with rare muscular dystrophies such as Ullrich dystrophy (COL6A2) may present with a mix of distal hypermobility, proximal weakness and contractures. Muscle weakness may be mistaken for joint hypermobility without thorough neurological examination. Individuals with Marfan syndrome (fibrillin 1; FBN1 gene) may have ligamentous laxity and reduced muscle mass, with limitation of elbow joint extension. It is important to exclude the vascular form of Ehlers–Danlos syndrome (EDS) (type IV; COL3A1) because of the propensity for arterial and organ rupture. Features such as skin translucency and excessive bruising, along with family history of sudden vascular death in early adulthood,16 are clues to a possible diagnosis of a vascular form of EDS. JHS may be part of the HDCT spectrum where the degree of skin and vascular involvement is
Journal of Paediatrics and Child Health (2014) © 2014 The Authors Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
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(a)
(b)
(d)
(e)
(c)
Fig. 1 Beighton score. Points are awarded for the following: (a) fifth-finger metacarpophalangeal joint extension >90° (one point for each side); (b) ability to touch thumb to forearm (one point for each side); (c) elbow extension >10° (one point for each side); (d) knee extension >10° (one point for each side); (e) ability to touch palms flat to floor with knees straight (one point). Scores ≥4 (out of 9) indicate generalised joint hypermobility.
less than in the other forms of EDS (Table 2), and a diagnosis of EDS hypermobility type (EDS-HT, previously called EDS type III) is often considered when hypermobility and mild skin involvement are present.14,19 The clinical features of JHS and EDS-HT are indistinguishable.20 When the Brighton criteria for JHS were defined, it was acknowledged that individuals with Marfan syndrome, osteogenesis imperfecta and other more severe forms of EDS may have symptoms of JHS, but these conditions were ‘excluded’.19 Since the Brighton conference, several new disorders associated with Marfan-like features and newer forms of EDS have been identified. Importantly, Loeys–Dietz syndrome (LDS) has been identified as an HDCT with specific facial dysmorphism (hypertelorism, bifid uvula, cleft palate), Marfanoid habitus, and generalised arterial tortuosity and risk of arterial rupture.21 As knowledge of this condition has increased, the LDS spectrum has broadened to include individ2
uals of normal stature and minimal facial dysmorphism with persistent arterial tortuosity risk. Joint hypermobility is very common in LDS, particularly in childhood.22 At least four different genes (TGFBR1, TGFBR2, TGFB2, SMAD3) have now been determined to cause LDS,23 emphasising the role of noncollagen extracellular matrix proteins and intracellular factors in causing HDCT associated with systemic symptoms. A few patients with JHS have been reported with deficiency of an extracellular glycoprotein called tenascin X due to loss of function of the TNXB gene, usually in conjunction with features of congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CYP21B gene deletion).17 Given that JHS may occur in association with several welldefined HDCTs that are difficult to distinguish clinically from EDS-HT, it is important to consider these diagnoses (Fig. 2) and refer, when appropriate, for further investigations such as echocardiographic and ophthalmological examination and
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Table 1
Brighton criteria for joint hypermobility syndrome
Major criteria • Beighton score of ≥4 • Arthralgia for longer than 3 months in four or more joints Minor criteria • Beighton score of 1, 2 or 3 • Arthralgia (>3 months) in one to three joints, back pain (>3 months), or spondylosis/spondylolysis/spondylolisthesis • Dislocation or subluxation in more than one joint, or in one joint on more than one occasion • Three or more soft tissue lesions (e.g. epicondylitis, tenosynovitis, bursitis) • Marfanoid habitus (tall, slim, span greater than height (>1.03 ratio), upper segment less than lower segment (16 weeks) may make chronic pain worse, as well as causing dependence.33 Some patients with chronic pain may benefit from pharmacological therapies beyond simple analgesia to modify pain perception, such as selective serotonin re-uptake inhibitors, tricyclic antidepressants, and anti-epileptics such as gabapentin, though these drugs should be used cautiously and not on a long-term basis. Pharmacological therapies do not provide longlasting symptom control in JHS and should not be relied on in isolation without a physical and psychological treatment plan.
Joint and soft tissue injury Joint instability and injury are common complaints in children with JHS, with the knee the most affected joint.9 Reduced joint proprioception, reduced muscle power,34 altered movement strategies,35 poor balance26 and reduced physical fitness,36 along
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A ru r teri pt al ur e
Cleft palate Bifid uvula Pectus Scoliosis BAV / ASD / PDS Allergy MVP Bowel Dysautonomia TEV Pes planus dislocations Osteopenia Blue CDH EDS-HT / sclerae
Uterine rupture Progeria
Bruising
JHS
Atrophic scars
Hearing loss
OI Fractures
Skin fragility
Fig. 2 Overlapping features in heritable disorders of connective tissue presenting with joint hypermobility. Adapted from Grahame.15 ASD, atrial septal defect; BAV, bicuspid aortic valve; CDH, congenital dysplasia of the hips; EDS, Ehlers–Danlos syndrome; EDS-HT, Ehlers–Danlos syndrome hypermobility type; JHS, joint hypermobility syndrome; MVP, mitral valve prolapse; OI, osteogenesis imperfecta; PDA, persistent ductus arteriosus; TEV, talipes equinovarus.
with underlying connective tissue fragility present in JHS, may all contribute to the increased risk of injury. Injury management should follow the usual course, with emphasis placed on addressing contributing factors that are amenable to change. Recovery from injury may take longer in individuals with JHS,37 particularly the recovery of muscular strength and endurance.27 Injuries should be treated promptly by clinicians with expertise in managing hypermobility and sports injuries to avoid the development of chronic symptoms.
Physical activity Participation in everyday activities is significantly reduced in children with JHS.26 Children with JHS report difficulties participating in school physical education classes,9 and reduced participation in sporting activities continues into adulthood.38 The relationship between hypermobility and gross motor skill proficiency is unclear in the general population, but hypermobility is disadvantageous in those children with developmental co-ordination disorder.39 Generalised joint hypermobilty may be advantageous in activities such as ballet or gymnastics. However, an increased incidence of pain and injury in individuals with JHS may prevent the child from progressing to higher levels within these fields.40 A thorough assessment of the child’s hypermobility and active joint stability will assist clinicians in guiding families in choosing physical activities that children can undertake with minimal pain and injury while still reaping the social and health benefits. Care should be taken with contact sports, particularly if the child is hypermobile in the cervical spine (extension range 90° 4
or more). Knee joint injuries are almost five times more likely to occur in hypermobile participants of contact sports,41 and finger injuries are common in ball sports such as netball.42 Individual non-contact activities such as swimming or Pilates are often recommended27; however, many children prefer team sports.
Hand function and handwriting Impaired hand function is a common disabling symptom in JHS,9,38 with handwriting difficulty reported in up to 40% of patients. Instability may be present at the interphalangeal, metacarpophalangeal and carpometacarpal joints of the thumb and the distal and proximal interphalangeal joints of the index and middle fingers. The wrist is often implicated. To compensate, students with JHS frequently adopt a palmar grasp, increasing the skin surface area on the writing implement with the index and middle fingers overlapped by the thumb. The resultant firm and immobile grasp restricts movement, as the muscles are engaged in supporting the joints, placing strain on the hand, the forearm and often the upper arm. Examples of these grips are seen in Figure 3.43 These static grasps contribute to muscle fatigue, pain, and decreased handwriting legibility, speed and endurance.9,44 Students with JHS may have difficulty producing written output required to meet classroom demands. Long-term handwriting difficulties may have significant negative implications for academic performance, learning and self-esteem.45 Specific techniques to assist with handwriting include using assistive equipment such as back cushions, footstools, slope boards and pen grips to ensure an ergonomic posture when writing. Splints and taping are used to provide external stability
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Table 2 Ehlers–Danlos syndrome classification and summary of major types17,18 Villefranche classification
Inheritance
Body parts involved
Features
Genes
Classical (I, II)
Autosomal dominant
Skin Joints
COL5A1, COL5A2 (>50%); COL1A1
Hypermobility (III)
Autosomal dominant
Vascular (IV)
Autosomal dominant
Joints Skin Gastrointestinal tract Central nervous system Vascular system Viscera Joints Skin
Fragility Hyperextensibility Atrophic scars Easy bruising Hypermobility Sprains, dislocations Generalised hypermobility Pain/fatigue Soft, doughy skin
COL3A1
Kyphoscoliotic (VIA)
Autosomal recessive
Joints Eyes Skin
Arthrochalasic (VIIA, VIIB)
Autosomal dominant
Joints Skin
Dermatosparaxis (VIIC)
Autosomal recessive
Skin
Arterial rupture Uterine rupture Bowel perforation Hypermobility, especially distal Acrogeria Excess bruising Thin, translucent skin Congenital, progressive Scoliosis Hypermobility Microcornea Scleral fragility – globe rupture Fragility, bruising Congenital hip dislocation Recurrent joint dislocation Hypermobility Hyperextensibility, fragility Severe fragility Sagging skin Premature rupture of membranes Herniae
Other rare forms Musculocontractural type (EDS VIB)
Autosomal recessive
Brittle cornea syndrome (EDS VIB)
Autosomal recessive
OCULAR Skin joints
Spondylocheirodysplastic
Autosomal recessive
Skin Joints ocular
Arthrogryposis Joint dislocation Joint laxity kyphoscoliosis hypotonia; skin laxity hydronephrosis Myopia, keratoconus, Brittle cornea Joint laxity Scoliosis Skin fragility Short stature; Small hands, finger contractures; Skin hyperelasticity; Joint hypermobility
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TNXB (10%), other unknown genes
PLOD1
COL1A1, COL1A2
ADAMTS2
CHST14; DSE
ZNF469; PRDM5
SLC39A13
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(a) Table 3 Baseline investigations and referrals to consider in patients with hypermobility24 • • • • • • •
Chromosome microarray Fragile X gene test, especially in developmental delay in males Urine metabolic screen Skeletal survey (if patient is of short stature) Echocardiogram Ophthalmological examination Non-invasive vascular imaging (magnetic resonance imaging/angiogram) • Referral for genetic testing to exclude identifiable heritable disorders of connective tissue
to distal joints, allow more fluid movement, and prevent or delay the onset of pain and fatigue. Despite a lack of published evidence, the use of splinting has been observed to reduce pain and improve endurance. In relation to curriculum access, frequent rest breaks are required, particularly during writing-intensive subjects and examination procedures. For students who experience pain within minutes of writing, alternative strategies such as accessing other students’ notes or using technology such as tablet devices or computers are required. Liaison with the school is important to ensure strategies can be implemented throughout the day. Classrooms may be timetabled close together or on the ground floor to limit the amount of walking between classes. Students are advised to use lockers and to have a second set of textbooks to avoid carrying heavy bags.
(b)
Fatigue Fatigue is a disabling symptom for the majority of children with JHS.10 Children with JHS often do not report fatigue unless questioned or objectively assessed, possibly because of difficulties describing it, or because they have lived with it for some time and do not realise what is normal. The cause of fatigue in this population remains unknown, and it is likely to be multifactorial in nature. Screening children with disabling fatigue for other conditions is often warranted. A diagnosis of chronic fatigue syndrome (CFS) is excluded by the presence of underlying JHS, but the standard multidisciplinary approach to CFS is usually beneficial.46 Poor sleep,47 muscle weakness48 and dysautonomia49 have all been shown to be associated with worse fatigue in JHS. Physiotherapy-based graded reconditioning programmes seem to be helpful, and anecdotally, aquatic physiotherapy seems efficacious for children with fatigue that interferes with their day-to-day activities. Cognitive–behavioural therapy including self-management and pacing advice is widely recommended, and involvement of a psychologist and the child’s school is important in sustaining improvement. Sleep dysfunction is also frequently observed in children with JHS9 and should be addressed, as it may potentiate chronic pain and fatigue.
Psychological interventions Patients with JHS are known to have fluctuating symptom patterns that can be unpredictable and disruptive to their 6
Fig. 3 Variations in pencil grip seen in children with joint hypermobility. (a) Lateral quadrupod pencil grasp. The thumb variably overlaps the index, third and fourth fingers, keeping the pencil in the palm of the hand. This is a firm and immobile grasp that prevents distal control of the fingers and can result in strain of the wrist and hand. Writing speed, endurance and legibility are affected by this type of grasp. (b) Lateral tripod pencil grasp. The thumb overlaps the index and middle finger, keeping the pencil in the palm of the hand. This is a static grasp that can cause muscle fatigue and pain with prolonged writing, resulting in impaired speed and legibility.
general functioning. ‘Boom and bust’ cycles are often established, where periods of relative symptom control can result in excessive activity, which can result in worsening symptoms and periods of inactivity, which in turn worsen symptoms. Patients, their families and their schools need to be educated about instituting a paced and graded activity programme that establishes a pattern of essential activities, including school and household tasks, that children need to be able to undertake before additional activities such as sports and recreation are added in a stepwise fashion. Psychological intervention to explore stressors and develop coping strategies for fatigue, chronic pain and anxiety is also essential in some patients.
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Summary Joint hypermobility is a relatively common condition. It is occasionally associated with a significant underlying HDCT, which may have other important organ involvements. These should be actively excluded by physicians seeing these patients. Up to a half of hypermobile patients will have significant symptoms justifying a diagnosis of JHS. A combination of physical and psychological therapies is usually successful in controlling these symptoms and limiting their impact on a young person’s life. Attention to education and empowerment of the patient and family are essential as part of the development of effective self-management strategies. To ensure accurate diagnosis and appropriate management, clinicians must consider the possibility of JHS when assessing patients whose primary symptoms are musculoskeletal but who also present extra-articular manifestations such as fatigue, generalised pain, gastrointestinal dysfunction, postural hypotension or dizziness, and skin fragility.
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15 Grahame R. Heritable disorders of connective tissue. Baillieres Best Pract. Res. Clin. Rheumatol. 2000; 14: 345–61. 16 Oderich GS, Panneton JM, Bower TC et al. The spectrum, management and clinical outcome of Ehlers–Danlos syndrome type IV: a 30-year experience. J. Vasc. Surg. 2005; 42: 98–106. 17 Bristow J, Carey W, Egging D, Schalkwijk J. Tenascin-X, collagen, elastin, and the Ehlers–Danlos syndrome. Am. J. Med. Genet. C. Semin. Med. Genet. 2005; 139C: 24–30. 18 Keer R, Simmonds J. Joint protection and physical rehabilitation of the adult with hypermobility syndrome. Curr. Opin. Rheumatol. 2011; 23: 131–6. 19 Grahame R, Bird HA, Child A. The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS). J. Rheumatol. 2000; 27: 1777–9. 20 De Paepe A, Malfait F. The Ehlers–Danlos syndrome, a disorder with many faces. Clin. Genet. 2012; 82: 1–11. 21 Loeys BL, Chen J, Neptune ER et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat. Genet. 2005; 37: 275–81. 22 Erkula G, Sponseller PD, Paulsen LC, Oswald GL, Loeys BL, Dietz HC. Musculoskeletal findings of Loeys–Dietz syndrome. J. Bone Joint Surg. Am. 2010; 92: 1876–83. 23 Van Laer L, Dietz H, Loeys B. Loeys–Dietz syndrome. Adv. Exp. Med. Biol. 2014; 802: 95–105. 24 Branson JA, Kozlowska K, Kaczynski KJ, Roesler TA. Managing chronic pain in a young adolescent girl with Ehlers–Danlos syndrome. Harv. Rev. Psychiatry 2011; 19: 259–70. 25 Tofts LJ, Elliott EJ, Munns C, Pacey V, Sillence DO. The differential diagnosis of children with joint hypermobility: a review of the literature. Pediatr. Rheumatol. Online J. 2009; 7: 1. 26 Schubert-Hjalmarsson E, Ohman A, Kyllerman M, Beckung E. Pain, balance, activity, and participation in children with hypermobility syndrome. Pediatr. Phys. Ther. 2012; 24: 339–44. 27 Simmonds JV, Keer RJ. Hypermobility and the hypermobility syndrome. Man. Ther. 2007; 12: 298–309. 28 Kemp S, Roberts I, Gamble C et al. A randomized comparative trial of generalized versus targeted physiotherapy in the management of childhood hypermobility. Rheumatology (Oxford) 2010; 49: 315–25. 29 Pacey V, Tofts L, Adams RD, Munns CF, Nicholson LL. Exercise in children with joint hypermobility syndrome and knee pain: a randomised controlled trial comparing exercise into hypermobile versus neutral knee extension. Pediatr. Rheumatol. Online J. 2013; 11: 30. 30 Birt L, Pfeil M, MacGregor A, Armon K, Poland F. Adherence to home physiotherapy treatment in children and young people with joint hypermobility: a qualitative report of family perspectives on acceptability and efficacy. Musculoskeletal Care 2013; 12: 56–61. 31 McCulloch R, Redmond A. The hypermobile foot. In: Hakim AJ, Keer R, Grahame R, eds. Hypermobility, Fibromyalgia and Chronic Pain. London: Elsevier, 2010; 255–67. 32 Tobias JH, Deere K, Palmer S, Clark EM, Clinch J. Hypermobility is a risk factor for musculoskeletal pain in adolescence: findings from a prospective cohort study. Arthritis Rheum. 2013; 65: 1107–15. 33 Crofford LJ. Adverse effects of chronic opioid therapy for chronic musculoskeletal pain. Nat. Rev. Rheumatol. 2010; 6: 191–7. 34 Fatoye F, Palmer S, Macmillan F, Rowe P, van der Linden M. Proprioception and muscle torque deficits in children with hypermobility syndrome. Rheumatology (Oxford) 2009; 48: 152–7. 35 Fatoye FA, Palmer S, van der Linden ML, Rowe PJ, Macmillan F. Gait kinematics and passive knee joint range of motion in children with hypermobility syndrome. Gait Posture 2011; 33: 447–51.
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36 Engelbert RHH, van Bergen M, Henneken T, Helders PJM, Takken T. Exercise tolerance in children and adolescents with musculoskeletal pain in joint hypermobility and joint hypomobility syndrome. Pediatrics 2006; 118: e690–6. 37 Briggs J, McCormack M, Hakim AJ, Grahame R. Injury and joint hypermobility syndrome in ballet dancers – a 5-year follow-up. Rheumatology (Oxford) 2009; 48: 1613–14. 38 Rombaut L, Malfait F, Cools A, De Paepe A, Calders P. Musculoskeletal complaints, physical activity and health-related quality of life among patients with the Ehlers–Danlos syndrome hypermobility type. Disabil. Rehabil. 2010; 32: 1339–45. 39 Jelsma LD, Geuze RH, Klerks MH, Niemeijer AS, Smits-Engelsman BC. The relationship between joint mobility and motor performance in children with and without the diagnosis of developmental coordination disorder. BMC Pediatr. 2013; 13: 35. 40 McCormack M, Briggs J, Hakim A, Grahame R. Joint laxity and the benign joint hypermobility syndrome in student and professional ballet dancers. J. Rheumatol. 2004; 31: 173–8. 41 Pacey V, Nicholson LL, Adams RD, Munn J, Munns CF. Generalized joint hypermobility and risk of lower limb joint injury during sport. Am. J. Sports Med. 2010; 38: 1487–97. 42 Smith R, Damodaran AK, Swaminathan S, Campbell R, Barnsley L. Hypermobility and sports injuries in junior netball players. Br. J. Sports Med. 2005; 39: 628–31. 43 Koziatek SM, Powell NJ. Pencil grips, legibility, and speed of fourth-graders’ writing in cursive. Am. J. Occup. Ther. 2003; 57: 284–8. 44 Kirby A, Davies R, Bryant A. Hypermobility syndrome and developmental coordination disorder: similarities and features. Int. J. Ther. Rehabil. 2005; 12: 431–7. 45 Wallen M, Bonney M, Lennox L. Interrater reliability of the handwriting speed test. Occup. Ther. J. Res. 1996; 17: 280–7. 46 National Institute for Health and Care Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. London: National Institute for Health and Care Excellence, 2007. NICE Clinical Guidelines, No. 53. 47 Voermans NC, Knoop H, van de Kamp N, Hamel BC, Bleijenberg G, van Engelen BG. Fatigue is a frequent and clinically relevant problem in Ehlers–Danlos syndrome. Semin. Arthritis Rheum. 2010; 40: 267–74. 48 Voermans NC, Knoop H, Bleijenberg G, van Engelen BG. Fatigue is associated with muscle weakness in Ehlers–Danlos syndrome: an explorative study. Physiotherapy 2011; 97: 170–4. 49 Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am. J. Med. 2003; 115: 33–40.
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Multiple Choice Questions 1. Joint hypermobility syndrome is a disorder affecting which of the following? a. The musculoskeletal system only b. The musculoskeletal system and the skin c. The musculoskeletal and cardiovascular systems d. The musculoskeletal and gastrointestinal systems e. Multiple organ systems Answer: e Joint hypermobility syndrome is a multisystem disorder with variable presentation across patients. Multiple system involvement may include the joints, the skin and the gastrointestinal, cardiovascular and autonomic nervous systems. 2. Children with joint pain caused by or related to hypermobility often describe which of the following? a. Pain worse with activity b. Pain worse in the morning c. Persistent joint swelling d. No improvement with rest e. Improvement with non-steroidal anti-inflammatory medications Answer: a Options b, c and e are all features of inflammatory joint disease and should be considered as differential diagnoses. Symptoms of joint pain in joint hypermobility syndrome usually improve with rest. 3. Important contributors to chronic fatigue in joint hypermobility syndrome include which of the following? a. Poor sleep, hypothyroidism, deconditioning b. Dysautonomia, anaemia, muscle weakness c. Poor sleep, deconditioning, depression d. Poor sleep, dysautonomia, muscle weakness e. Coeliac disease, poor sleep, deconditioning Answer: d The others are all direct causes of fatigue and not regularly associated with joint hypermobility syndrome.
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