Joint hypermobility syndrome in childhood. A not so benign multisystem disorder?

[Guest guest]

Joint hypermobility syndrome in childhood. A not so benign multisystem

disorder? *N. Adib, K. Davies, R. Grahame, P. Woo* and *K. J. Murray1 *

Rheumatology Unit, Great Ormond Street Hospital, London, UK. 1 Present

address: Rheumatology Department, Princess Margaret Hospital for Children,

Perth, WA, Australia.

Correspondence to: N. Adib, Clinical Research Fellow, Arthritis Research

Campaign Unit, School of Epidemiology, Stopford Building, University of

Manchester, Oxford Road, Manchester M13 9PT, UK. E-mail:

navid.adib@...

Abstract Top

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#top>

Abstract

Introduction

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BDY>

Methods

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC1>

Results

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC2>

Discussion

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC3>

References

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIBL>

*Objectives*. Joint hypermobility (JH) or 'ligamentous laxity' is felt to be

an underlying risk factor for many types of musculoskeletal presentation in

paediatrics, and joint hypermobility syndrome (JHS) describes such disorders

where symptoms become chronic, often more generalized and associated with

functional impairment. Clinical features are felt to have much in common

with more severe disorders, including Ehlers¨CDanlos syndrome (EDS),

osteogenesis

imperfecta and Marfan syndrome, although this has not been formally studied

in children. We defined the clinical characteristics of all patients with

joint hypermobility-related presentations seen from 1999 to 2002 in a

tertiary referral paediatric rheumatology unit.

*Methods*. Patients were identified and recruited from paediatric rheumatology

clinic and ward, and a dedicated paediatric rheumatology hypermobility

clinic at Great Ormond Street Hospital. Data were collected retrospectively

on the patients from the paediatric rheumatology clinics (1999¨C2002) and

prospectively on patients seen in the hypermobility clinic

(2000¨C2002). Specifically,

historical details of developmental milestones, musculoskeletal or soft

tissue diagnoses and symptoms, and significant past medical history were

recorded. Examination features sought included measurements of joint and

soft tissue laxity, and associated conditions such as scoliosis, dysmorphic

features, cardiac murmurs and eye problems.

*Results*. One hundred and twenty-five children (64 females) were included

on whom sufficient clinical data could be identified and who had clinical

problems ascribed to JH present for longer than 3 months. Sixty-four were

from the paediatric rheumatology clinic and 61 from the hypermobility

clinic. No differences were found in any of the measures between the two

populations and results are presented in a combined fashion. Three-quarters of

referrals came from paediatricians and general practitioners but in only 10%

was hypermobility recognized as a possible cause of joint complaint. The

average age at onset of symptoms was 6.2 yr and age at diagnosis 9.0 yr,

indicating a 2- to 3-yr delay in diagnosis. The major presenting complaint

was arthralgia in 74%, abnormal gait in 10%, apparent joint deformity

in 10% and

back pain in 6%. Mean age at first walking was 15.0 months; 48% were

considered 'clumsy' and 36% as having poor coordination in early childhood.

Twelve per cent had 'clicky' hips at birth and 4% actual congenital

dislocatable hip. Urinary tract infections were present in 13 and 6% of the

female and male cases, respectively. Thirteen and 14%, respectively, had speech

and learning difficulties diagnosed. A history of recurrent joint sprains

was seen in 20% and actual subluxation/dislocation of joints in 10%. Forty

per cent had experienced problems with handwriting tasks, 48% had major

limitations of school-based physical education activities, 67% other

physical activities and 41% had missed significant periods of schooling

because of symptoms. Forty-three per cent described a history of easy bruising.

Examination revealed that 94% scored [image: ¡Ý]4/9 on the Beighton scale for

generalized hypermobility, with knees (92%), elbows (87%), wrists (82%),

hand metacarpophalangeal joints (79%), and ankles (75%) being most

frequently involved.

*Conclusions*. JHS is poorly recognized in children with a long delay in the

time to diagnosis. Although there is a referral bias towards joint symptoms,

a surprisingly large proportion is associated with significant neuromuscular

and motor development problems. Our patients with JHS also show many overlap

features with genetic disorders such as EDS and Marfan syndrome. The delay

in diagnosis results in poor control of pain and disruption of normal home

life, schooling and physical activities. Knowledge of the diagnosis and

simple interventions are likely to be highly effective in reducing the

morbidity and cost to the health and social services.

KEY WORDS: Joint hypermobility, Benign joint hypermobility syndrome,

Heritable disorders of connective tissue, Mechanical pain

Introduction Top

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#top>

Abstract

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#ABS>

Introduction

Methods

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC1>

Results

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC2>

Discussion

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC3>

References

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIBL>

Children possess an inherently greater range of motion in their joints than

adults, with a gradual reduction in this range observed with age

[1<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB1>,

2 <http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB2>].

The prevalence of hypermobility in children as a phenomenon [as opposed to

joint hypermobility syndrome (JHS), i.e. symptomatic hypermobility] has been

measured in a number of studies previously and, depending on the age

or ethnicity

of the study population or the inclusion criteria, has been reported to be

between 2.3 and 30%

[2¨C8<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB2><htt\

p://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB3><http://rheum\

atology.oxfordjournals.org/cgi/content/full/44/6/744#BIB4><http://rheumatology.o\

xfordjournals.org/cgi/content/full/44/6/744#BIB5><http://rheumatology.oxfordjour\

nals.org/cgi/content/full/44/6/744#BIB6><http://rheumatology.oxfordjournals.org/\

cgi/content/full/44/6/744#BIB7><http://rheumatology.oxfordjournals.org/cgi/conte\

nt/full/44/6/744#BIB8>].

Such high prevalence rates imply that hypermobility as a measured phenomenon

in a significant majority of children will not normally lead to symptoms

requiring medical attention. There are a number of studies that show the

association between benign joint hypermobility syndrome and chronic health

complaints in adults. Whilst arthralgia and chronic regional pain were the

predominant symptoms, there were numerous extra-articular manifestations

with dysautonomia and peripheral neuropathy, hernia and uterine/rectal

prolapse, depression and anxiety, and chronic pain syndromes, to name a few

[9 <http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB9>,

10 <http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB10>].

Numerous extra-articular manifestations of JHS have been similarly reported

in children, including but not limited to chronic constipation and

encopresis, enuresis and urinary tract infections (UTI), higher skin

extensibility, lower systemic blood pressure, lower bone quantitative

ultrasound measurements, chronic fatigue syndrome, temporomandibular

joint disease,

fibromyalgia, and gross motor developmental delay

[11¨C14<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB11><\

http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB12><http://r\

heumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB13><http://rheumatol\

ogy.oxfordjournals.org/cgi/content/full/44/6/744#BIB14>

]. These studies also reported association between joint hypermobility and

musculoskeletal disorders in children, whilst others did not find such a

relationship

[15<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB15>

].

The aim of this study was to characterize the historical and current

clinical profile of a cohort of children with symptomatic joint

hypermobility who had been referred to a paediatric rheumatology tertiary

referral centre.

Methods Top

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Abstract

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#ABS>

Introduction

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BDY>

Methods

Results

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC2>

Discussion

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC3>

References

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIBL>

*Study design and setting*

The study was carried out in the outpatients and inpatients facilities of a

paediatric rheumatology unit at a tertiary referral centre. The patients

were recruited from two sources. The first group were the patients referred

by general paediatricians or general practitioners, paediatric and adult

rheumatologists, orthopaedic surgeons, physiotherapists, and the patient's

own family to a dedicated hypermobility clinic at Great Ormond Street Hospital

(GOSH), for whom data were collected prospectively (2000¨C2002). The second

group of patients was identified by conducting searches in the electronic

databases of the paediatric rheumatology department at GOSH. The latter

group had been cared for in other paediatric rheumatology clinic or ward,

and the relevant information was collected through review of their

hospital case-notes

(1999¨C2002).

*Patients and case ascertainment*

Inclusion criteria consisted of age <18 yr, the presence of joint

hypermobility diagnosed by a consultant paediatric rheumatologist, and

adverse symptom(s) related to the hypermobile joint(s). Patients were

excluded if they were known or considered to have any other pathological

condition with hypermobility as a known feature (e.g. specific collagen

disorders, chromosomal abnormalities, metabolic disease), or if there was

coexisting rheumatological illness which could account for at least some of

their musculoskeletal symptoms.

*Data collection and analysis*

For the prospective cohort, relevant patient and family history was

systematically sought by the use of a study questionnaire, and details of a

complete systematic examination, including the musculoskeletal system, were

similarly recorded on the study data collection sheets. Joint hypermobility

was looked for in all of the possible joints, and the details of Beighton

score

[16<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB16>]

were recorded. For the retrospective cases, the same study questionnaire was

completed using patient case-notes. Furthermore, information regarding

previous referrals, diagnoses and treatments were enquired about and

included. The management plan and interventions were similarly recorded and

where patients were followed up for their hypermobility problem the response

to intervention was sought and documented.

For statistical analysis the StataTM 8.2 software program (Stata, College

Station, TX, USA) was used. To compare the prevalence of congenital

dislocatable hip (CDH), UTI, urinary tract dysfunction (vesico-ureteric

reflux) and inguinal hernia with that of the normal population, 95%

confidence intervals (CI) around the proportions in our cohort were

calculated. The difference was deemed significant if the previously quoted

rates were not within this interval. For comparing the median age of the

cases with lower back pain with the cases without lower back pain,

non-parametric tests were used. Similarly, to test the hypothesis that

the degree

of hypermobility varies with age, individual Beighton scores were

calculated. The cases were divided into four age groups (Fig.

3<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#FIG3>)

and non-parametric tests (Kruskal¨CWallis) were used to compare the median

for the Beighton score in each age subgroup.

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FIG. 3. Beighton score by age groups. The groups were not significantly

different in terms of hypermobility score.

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FIG. 1. Percentage of cases for height and weight centiles. The

anthropometric measurements in this cohort followed nearly those of their

source population.

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FIG. 2. Frequency and percentage of cases categorized by their Beighton

score. Whilst inclusion in the study did not require more than 1 joint to be

involved, the majority of the cases had high scores.

Approval was obtained from the hospital's ethics committee, and all

patients' parents/guardians were required to give informed consent to be

included in the study.

Results Top

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Abstract

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#ABS>

Introduction

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BDY>

Methods

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC1>

Results

Discussion

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC3>

References

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIBL>

One hundred and eighty-nine patients were assessed for inclusion in the

study, of whom 125 satisfied the inclusion criteria. All of the patients'

parents/guardians who were approached to take part in the study agreed to

join. For the majority of the patients complete data were available for all

variables. However, in some cases part of the questionnaire was not

answered, or, in the retrospective cases, some data were not available. As a

result, where relevant, numbers are expressed as the fraction of available

cases. Table

1<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL1>summariz\

es

the demographic characteristics in

this cohort. This was a predominantly Caucasian patient group, with a slight

female majority. The 'Other White' category consisted of two Middle Eastern

Arabs, one Egyptian, one Moroccan, one Iranian, one Turk and two Greek

Cypriots. The 'Mixed' category included one Anglo-Mauritian, one

Anglo-Pakistani, one Caucasian-Afro-Caribbean, two Caucasian-Moroccans and

three Caucasian-unknowns. The median assessment age for the purposes of this

study was one of mid-childhood to later childhood. The anthropometric data

are summarized in Fig.

1<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#FIG1>

, with height and weight distributions similar to that of a normal reference

population. The bulk of the referrals (73.6%) were made by the children's

general paediatrician or practitioner, but in only <10% (9/92) of cases was

hypermobility given by them as the cause of symptoms (Table

2<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL2>

).

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TABLE 1. Demographics and patient characteristics of 125 patients with

benign joint hypermobility syndrome

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TABLE 2. Referral details and the number of cases

Table

3<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL3>illustra\

tes

the age characteristics of this cohort in relation

to symptom onset, diagnosis and referral. In the majority there was a

significant time lapse between the onset of symptoms and the establishment

of hypermobility as the cause, whilst this interval is much shorter when

comparing age at diagnosis with age at first attendance at the paediatric

rheumatology facilities.

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TABLE 3. Ages at onset, first attendance and diagnosis (yr)

Table

4<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL4>summariz\

es

other associated clinical characteristics in

this patient group. Clumsiness and poor coordination, easy bruising, clicky

joints and family history of significant or problematic joint laxity were

reported most frequently. Family history of joint laxity in a first degree

relative included nine fathers, 18 mothers, five parent pairs, 15

parent¨Csibling pairs, three parents¨Csibling trios and seven siblings. This

history was also present in 24 second-degree relatives. The mean age of

first walking in this cohort was 15.0 months (range 8.5¨C36.0), which is

considerably later than the usual average age reported in most populations,

which is between 11 and 12 months

[17<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB17>

].

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TABLE 4. Associated clinical history in proportions of cases where this

information was available

The prevalence of CDH was 4.8% (95% CI 1.6¨C10.8%), significantly higher in

this cohort than the 1% reported in the normal population

[18<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB18>].

The proportions having a history of UTI were measured in each gender. The

mean for the females was 13.2% (95% CI 5.5¨C25.3%) and that for males was 6%

(95% CI 1.2¨C16.2), both significantly greater than the rates in normal

population: 1% for boys and 2¨C5% for girls

[19<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB19>

].

Other clinical history, such as inguinal hernia (4%, 95% CI 1¨C9.8%) and

urinary tract dysfunction (4%, 95% CI 0.6¨C8.6%), although possibly increased

in occurrence amongst our cohort, did not reach significance when compared

with rates (1¨C2 and 1%, respectively) in the normal population

[20<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB20>],

perhaps as a result of small numbers. When other medical history was sought,

there were 12 cases (10%) with asthma. This parallels the prevalence of this

disorder (12¨C24%) amongst the source paediatric population

[21<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB21>

].

Joint pain followed by coordination problems and reduced joint movement

range, were the most common presenting features in this patient group (Table

5 <http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL5>).

Knees and ankles were the most frequently reported joints with adverse

symptoms. Although pain in the spine was recorded in 23 patients, this was a

major presenting complaint in only seven (5.6%). The median age of patients

with lower back pain was significantly higher than that of cases free of

back pain (9.0 *vs* 6.0 yr, *P* = 0.04).

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TABLE 5. Main presenting complaints in 125 cases with JHS

Exercise-related pain and anterior knee pain were reported with

disproportionately

greater frequency than any other symptoms in this cohort (Table

6<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL6>),

whilst joint swelling and back and foot pains came next in frequency. In all

of the cases reporting exercise-related pain, the pain occurred within 24 h

of activity. Immediate postexercise pain was reported in 52/80, with 47/80 and

40/80 reporting late evening and morning after pain, respectively. Joint

stiffness was present in almost one-third, and among the 41 reporting joint

swelling 18 also reported joint stiffness. One-third also reported sleep

disturbance due to musculoskeletal symptoms. More than half of patients

reported missing school, and a similar proportion did not take part in

physical education on a regular basis because of the symptoms.

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TABLE 6. Clinical symptoms and associated features in the proportions of

cases for whom this information was available

Tables

7<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL7>and

8

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL8>demonstra\

te

the extent to which investigations and

treatment had been carried out prior to treatment. With the exception of

plain radiographs revealing anatomical abnormalities (two scoliosis, one

dysplasia, one bifid rib and one transitional L5 vertebra), the majority of

these investigations were either normal or reported an incidental and

transient abnormality. Reported abnormalities on MRI scan consisted of

possible discitis at multiple spinal levels, mild gluteal wasting, and

subdural haemorrhage without any evidence of blood vessel aneurysm, in one

case each. Positive bone scintigraphy results included mild increased tracer

uptake at the third lumbar vertebra, and an ankle, in two separate cases.

Amongst other investigations were karyotype and specific gene testing

(fragile X, Marfan syndrome, hereditary sensorimotor neuropathy and

Beckwith¨CWiedemann syndrome), skin and muscle biopsy, pH-probe and barium

meal, electromyography and nerve conduction studies, echocardiography and

various urine and blood metabolic screens, the results of which were all

normal. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol were

the two most frequently used medications, only 21/51 patients reporting any

benefit from NSAIDs. Steroid courses and sulphasalazine were used in four

separate cases, without obvious benefit.

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TABLE 7. Investigations performed prior to referral and diagnosis

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TABLE 8. Treatment received before being seen by the paediatric

rheumatologist

Many patients had seen local therapists prior to their referral. This

included physiotherapy in 49%, occupational therapy in 13% and podiatry in

11%.

Pain on examination was elicited most frequently in the knees, ankles and

hips, in that order, these joints also featuring as having the highest rate

for increased movement range (Table

9<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL9>

). The joint movement range was most frequently decreased in the

thoracolumbar region. The Beighton score at assessment was used as a measure

of hypermobility. The distribution of the Beighton score was skewed towards

the higher range and is presented in Fig.

2<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#FIG2>.

There was a predilection for the three highest categories, 61/90 cases

scoring [image: ¡Ý]7. In the majority of patients without a formal Beighton

score, the presence or absence of ability to perform forward bending (to put

the hands on the floor) was the item omitted. In order to assess if

hypermobility was highest at any age, the cases were divided into four age

groups (Fig.

3<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#FIG3>

) and the medians for the Beighton scores were compared. The trend seems to

be that of decreasing score with age, although there was an increase in the

'pubertal' age quartile. Using non-parametric tests for the equality of the

populations (Kruskal¨CWallis test), the latter age group was not any different

in Beighton score compared with the rest of the cases (median 7.3 for

both, [image:

{chi}]2 = 0.021 with 1 degree of freedom, *P* = 0.88), nor was there any

significant difference in this variable between the four age groups ([image:

{chi}]2 = 6.3 with 3 degrees of freedom, *P* = 0.08).

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TABLE 9. Joint examination results in proportions of cases where this

information was available

Table

10<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL10>summar\

izes

the associated clinical findings of this study

group. The majority of the cases had pes planus, with muscle weakness as the

next common finding. Furthermore, muscle wasting was evident in more than a

quarter of cases where this was assessed. Of those cases with Marfanoid body

habitus, 7/10 had arachnodactyly and two had a heart murmur. The majority of

the cases with high-arched palate (4/5) and pectus carinatum (2/3) were not

Marfanoid, although the numbers were very small.

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TABLE 10. Associated clinical features on examination in the proportion of

cases where this information was available

Limited information was available at the time of reporting this cohort

regarding subsequent management and referrals. Fourteen patients required

inpatient hospital admission and an intensive rehabilitation programme.

Formal physiotherapy and home exercise programme have been documented in 69

and 86 cases, respectively; 51 reporting definite improvement. The basis of

the physical therapy was a very gradual reconditioning and re-establishment of

normal muscle power, by means of isometric exercises, and power building

activities. Where joint contractures and loss of movement range were

encountered, appropriate splints alongside stretching (active and passive)

exercises were carried out to improve mobility. Of 43 cases referred for

podiatry evaluation and management, 27 reported some benefit, whilst 13

denied any improvement (three were awaiting foot orthoses).

Discussion Top

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#top>

Abstract

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#ABS>

Introduction

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BDY>

Methods

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC1>

Results

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC2>

Discussion

References

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIBL>

The aim of this study was to characterize the historical clinical referral

patterns, investigation details and treatment in a paediatric cohort with

symptomatic joint hypermobility.

This cohort contains cases with more severe end of the spectrum of JHS. It

represents an important group of children whose persistent symptoms and loss

of function have caused a great deal of anxiety amongst both family and the

health professionals, requiring the utilization of significant time and

resources. Their demographic and anthropometric characteristics are not

dissimilar from their normal source population (Table

1<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#TBL1>and

Fig.

1 <http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#FIG1>).

Referral patterns and the time delay between symptom onset and paediatric

rheumatologist assessment suggest that in most cases a timely connection

between symptomatology and the hypermobility as a cause was not established. In

contrast, the short interval between referral date and identification of

joint hypermobility as the cause for their adverse symptoms indicates that

this diagnosis can be readily made in the clinical setting, provided that

the required skill and knowledge are present. Indeed, historical features of

this symptom complex (e.g. its intimate relationship with physical activity

and its characteristic worsening after exercise), along with the findings on

thorough clinical examination, are sufficient in nearly all cases to make

the correct diagnosis. This obviates the need for the costly, sophisticated

and mostly unnecessary investigations meted out to many children in this

series.

Clumsiness, poor coordination and late walking represent difficulties with

fine and gross motor development and may be related to the central nervous

system or proprioceptive control. The relatively high rate of learning

difficulties, dyslexia and dyspraxia also suggests possibility of central

nervous system involvement in this condition, although in the absence of

scientific evidence these observations should merely serve to suggest areas

for future research. The rates for CDH and UTI were significantly higher

amongst this cohort, whilst for hernia, urinary tract dysfunction and heart

murmur the results did not reach significance, possibly as a consequence of

insufficient case numbers. These observations suggest that, in addition to

the more obvious musculoskeletal features in joint hypermobility, other

organ systems are clearly involved, a finding also reported by others in

hypermobile adults and children

[22<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB22>,

23 <http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB23>].

Boys with generalized joint hypermobility have been found to have

constipation almost five times as often and faecal soiling twice as often as

controls, whilst urinary incontinence and infections were more prevalent in

girls with this condition

[24<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB24>].

Others showed higher skin extensibility, lower quantitative ultrasound

measurements in bones, and significantly increased urinary excretion of

collagen degradation products compared with the reference group

[25<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB25>].

The collagen content of the umbilical cords from newborns with CDH was

reduced in comparison with controls, and the collagen III/I ratio was

increased. Mutations in the fibrillin genes are found in a proportion of Marfan

syndrome and congenital contractural arachnodactyly

[26<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB26>

] and several mutations in collagen genes have been described in

osteogenesis imperfecta

[27<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB27>],

two conditions sharing overlapping clinical features with JHS

[16<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB16>,

28 <http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB28>]

as well as an autosomal dominant mode of inheritance. There were many shared

clinical features between our cohort and other heritable disorders of

connective

tissue (HDCT), although such characteristics (e.g. blue sclerae,

arachnodactyly) were not uniformly present in every case. Such heterogeneity

in the phenotype may be explained by gene polymorphism, incomplete

expression and/or penetrance, not dissimilar to other HDCTs. A family

history of joint laxity in the first-degree relatives was present in 63% of

our cohort. In addition, there were 24 (27%) second-degree relatives with this

history and a significant number of kindreds. These findings favour a

dominant mode of inheritance.

One of the main characteristics in the reported symptoms from this group is

its intimate association with exercise. Although joint stiffness was

reported in a minority, resting relieved the symptoms. This is in contrast

to the inflammatory rheumatological conditions where resting or inactivity

promotes 'gelling' or stiffness. Exercise-induced pain is not exclusive to

the 'mechanical' conditions, however, and may be observed in the

inflammatory condition, e.g. juvenile idiopathic arthritis. Similar in these

two conditions is perhaps disuse atrophy in the muscles, which may also

explain at least some of the coordination problems encountered in our

cohort. Repetitive pain-related muscular inhibition can result in reduced

muscle bulk, with resultant muscle deconditioning and loss of movement range

in joints. Furthermore, loss of motion at certain joints or areas is seen

(especially lumbar spine, but also tendo-achillis or gastrocnemii), which

may represent post-traumatic response or an 'adaptive postural stabilizing'

response. Tenderness and pain on examination is an important finding,

implying that such a feature does occur in JHS (as it does in

inflammatory arthritides)

and may occur for many reasons, such as tissue sensitivity, recent

sprain/strain injury, or an exaggerated perceived discomfort. Another aspect

of reduced exercise tolerance is the impact on play and social activities. A

significant proportion of our group did not engage in routine exercise, such

as physical education at school. Indeed, a significant number did not

attend school

altogether, this adding support to our observation regarding the profound

impact of this condition on the child's function. In addition, pain

amplification was perceived to be present by the clinician in 21% of the

cases. The relationship between joint hypermobility and chronic pain is well

known and has been frequently reported

[29¨C31<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB29><\

http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB30><http://r\

heumatology.oxfordjournals.org/cgi/content/full/44/6/744#BIB31>

].

Joint hypermobility is common in children, although in a small proportion it

may manifest as pathology, resulting in morbidity and loss of function. It

is of great importance to promote the knowledge of this common condition at

all levels of health-care provision. Further research into the genetic

aspects of this disorder will aid with prognosis and in the counselling of

families. Finally, the variable response rate to physiotherapy,

occupational therapy

and podiatry seen amongst this cohort highlights the heterogeneity of the

condition, and calls for the pressing need to conduct well-designed

prospective therapeutic trials.

The authors have declared no conflicts of interest.

References Top

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#top>

Abstract

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#ABS>

Introduction

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#BDY>

Methods

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC1>

Results

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC2>

Discussion

<http://rheumatology.oxfordjournals.org/cgi/content/full/44/6/744#SEC3>

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Submitted 21 October 2004; revised version accepted 24 December 2004.

--

" Life- Like the flutter of wings... feel your hollow wings rushing... " (AFI-

Silver and Cold).

my Flight in life is a metamorphosis of growth and this flutter of wings is

within me awaiting to find a space to find it's flow...