Association Between Generalized Joint Hypermobility and Anxiety Disorders in Children: A Case-Control Study

Abstract

Background:

Generalized Joint Hypermobility (GJH) is defined as a range of joint motion exceeding normal limits in multiple joints and is relatively common in children. Although often asymptomatic, GJH has been increasingly linked to psychological comorbidities, especially anxiety. While adult studies have highlighted these connections, pediatric-specific research remains limited.

Objectives:

This study aimed to evaluate the association between GJH and the prevalence of anxiety disorders in school-aged children using validated clinical and psychological measures.

Methods:

A case-control study was conducted among 3920 children aged 8 to 15 years in Isfahan, Iran (2021-2023). The Beighton scoring was used to identify children with GJH (score ⩾ 6), yielding 634 cases. An age- and sex-matched control group of 650 children without GJH was selected. Anxiety was assessed using the validated Spence Children Anxiety Scale (SCAS), covering separation anxiety, social phobia, panic/agoraphobia, specific phobia, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and generalized anxiety disorder (GAD). Logistic regression assessed associations between GJH and anxiety outcomes.

Results:

Children with GJH had significantly higher odds of separation anxiety (odds ratio [OR] = 4.49; confidence interval [CI]: 2.39-8.43), social phobia (OR = 4.32; CI = 2.40-7.75), panic disorder/agoraphobia (OR = 3.46; CI = 1.30-9.21), and GAD (OR = 2.87; CI = 1.10-7.47). ADHD, specific phobia, and OCD showed no significant differences between groups (P > .05).

Conclusion:

This study suggests a strong association between GJH and specific anxiety disorders in children. Given the ease of identifying GJH, psychological screening in this population may be a valuable preventive strategy.

Introduction

Joint hypermobility refers to an excessive range of motion in joints beyond age-appropriate norms. In children, this trait is frequently encountered and is considered benign in many cases. However, growing evidence suggests that hypermobility particularly when widespread may be associated with both physical symptoms and psychological distress. Generalized Joint Hypermobility (GJH) is now recognized as distinct from symptomatic hypermobility syndromes like Hypermobile Ehlers-Danlos Syndrome (HEDS) and Hypermobility Spectrum Disorders (HSD), per the 2017 International Classification of Ehlers-Danlos Syndrome (EDS).^1,2

The Beighton score remains the standard screening tool for detecting GJH, offering a practical method for quantifying hypermobility. A Beighton score ⩾6 is considered indicative of GJH in children, given their higher baseline joint flexibility compared with adults.^3,4 While GJH is often asymptomatic, studies suggest that it may serve as a biological marker for underlying dysautonomia, proprioceptive dysfunction, or even central sensitization syndromes that affect mood and cognition.^5-7

Adults with HEDS or HSD have been consistently shown to experience higher rates of psychiatric comorbidities, particularly anxiety, depression, and panic disorder.^8,9 However, pediatric studies are sparse, and those that exist often conflate GJH with symptomatic conditions, making it difficult to assess the true relationship between asymptomatic joint hypermobility and anxiety in children.

Eccles et al ¹⁰ demonstrated that adolescents with GJH were more likely to experience depression and anxiety by late adolescence. Bulbena et al also noted elevated ADHD and autism spectrum disorder (ASD) rates in hypermobile children. ¹¹ However, most studies lack a clear distinction between GJH and syndromic hypermobility and rely on retrospective or registry-based data.

In light of this gap, we conducted a large-scale, prospective, case-control study to explore the association between clinically confirmed GJH and anxiety disorders in children aged 8 to 15 years using the validated Spence Children Anxiety Scale (SCAS), which allows granular analysis of multiple anxiety subtypes.

Materials and Methods

Study design and setting

This was a school-based, observational, matched case-control study conducted between January 2021 and August 2023 in Isfahan, Iran. The study received ethical approval from the Isfahan University of Medical Sciences Research Ethics Committee (IR.MUI.REC.1400.560).

Participants and sampling

The target population comprised schoolchildren aged 8 to 15 years. A 2-stage stratified cluster random sampling technique was used. First, schools were randomly selected from different socioeconomic zones. Then, students were randomly chosen proportionally from each stratum. Written informed consent was obtained from all parents or legal guardians.

The inclusion criteria include:

• Age 8 to 15 years.

• Consent from parent/guardian.

• Attendance at selected schools.

The exclusion criteria include:

• Known chronic medical conditions (neurological, metabolic, rheumatologic, psychiatric, or immunologic disorders).

• History of recent trauma affecting joint examination.

• Lack of parental consent.

Assessment of Generalized Joint Hypermobility

All 3920 children underwent physical examination, first by a pediatrician and then by a pediatric rheumatologist with experience and skills in musculoskeletal evaluation. The Beighton score was used to assess joint laxity. The scoring includes:

• Passive dorsiflexion of the fifth finger >90° (2 points).

• Passive thumb apposition to forearm (2 points).

• Elbow hyperextension >10° (2 points).

• Knee hyperextension >10° (2 points).

• Forward trunk flexion with palms on the floor (1 point).

Children scoring ⩾6 out of 9 were classified as having GJH based on pediatric thresholds. ⁴ A total of 634 students were diagnosed with GJH; all of them were re-evaluated by another pediatric rheumatologist and their disorder was confirmed. A total of 634 students met this criterion and were included as cases.

Control group

From the remaining children without GJH (score < 6), 650 were selected by simple random sampling. Controls were matched for age and sex with the GJH group.

Anxiety assessment: Spence Children Anxiety Scale tool

The SCAS, parent-report version, was used to evaluate anxiety symptoms. This 38-item scale covers 6 anxiety domains: separation anxiety, social phobia, panic/agoraphobia, specific phobia, obsessive-compulsive disorder (OCD), and generalized anxiety disorder (GAD), with additional items for ADHD screening. ¹²

Each item is rated on a 4-point Likert scale (0 = never, 3 = always). Age- and gender-specific cut-off scores validated in Iranian children were applied. ¹² The SCAS has demonstrated excellent psychometric properties in cross-cultural contexts, including internal consistency (Cronbach’s alpha = 0.86) and construct validity.

Statistical analysis

Data were analyzed using IBM SPSS v26. Descriptive statistics summarized demographic and clinical variables. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between GJH and each anxiety subtype. Models were adjusted for age and gender. A Bonferroni correction was applied to control for multiple testing. Statistical significance was set at P < .05.

Results

Of the 3920 students assessed, 634 (16.2%) were diagnosed with GJH based on a Beighton score of ⩾6. These children were categorized as the case group. The control group comprised 650 students with a Beighton score <6, matched for age and sex.

Demographic profile

• Mean age of participants: 10.5 ± 2.3 years.

• Sex distribution: 51.1% female in both groups.

• No statistically significant difference in BMI or socioeconomic status between groups.

Beighton scores

• Mean Beighton score in the GJH group: 7.2 ± 0.9.

• Mean Beighton score in the control group: 2.1 ± 1.2.

Prevalence of anxiety disorders

As shown in Tables 1 and 2, there was a statistically significant association between GJH and separation anxiety in both girls and boys (OR = 4.6, P < .05, and OR = 4.4, P < .05, respectively), with an overall OR of 4.49 (95% CI = 2.39-8.43). In addition, GJH was significantly associated with social phobia in both girls and boys (OR = 5.9, P < .05, and OR = 3, P < .05, respectively), with a combined OR of 4.32 (P < .05, 95% CI = 2.40-7.75). There was also a significant association between GJH and panic disorder or agoraphobia in both genders (OR = 3.46, P < .05, 95% CI = 1.30-9.21). Furthermore, no significant association was found between GJH and ADHD in both girls and boys (OR = 1.85, P > .05, and OR = 2.08, P > .05, respectively). However, no significant associations were found between GJH and specific phobia or OCD (P > .05). There was also a significant association between GJH and generalized anxiety in both genders (OR = 2.87, P < .05, 95% CI = 1.10-7.47).

Table 1.

Prevalence of anxiety disorders among children with and without GJH.

Variables		Female				Male				Combined
		Case	Control	OR	P	Case	Control	OR	P	OR	95% CI
SP	Yes	105	32	4.6	<.05	94	28	4.4	<.05	4.49	2.39-8.43
	No	233	313			202	277
Soci. phob	Yes	128	32	5.9	<.05	98	43	3.0	<.05	4.32	2.40-7.75
	No	210	313			198	262
P/A phob	Yes	43	13	3.72	<.05	28	10	3.0	<.05	3.46	1.30-9.21
	No	295	332			268	295
S. phob	Yes	25	23	1.12	>.05	20	18	1.16	>.05	1.13	0.47-2.74
	No	313	322			276	187
OCD	Yes	19	17	1.15	>.05	21	23	0.94	>.05	1.03	0.42-2.57
	No	319	328			275	282
ADHD	Yes	16	9	1.85	>.05	12	5	2.54	>.05	2.08	0.54-7.97
	No	322	336			284	300
GA	Yes	38	14	2.99	<.05	27	11	2.68	<.05	2.87	1.10-7.47
	No	300	331			269	294

Abbreviations: ADHD, attention deficit/hyperactivity disorder; GA, generalized anxiety; OCD, obsessive compulsive disorder; P/A phob, panic or agoraphobia; Soci. phob, social phobia; SP, separation anxiety; S. phob, specific phobia.

Table 2.

Prevalence and adjusted odds ratios of anxiety disorders among children with and without GJH.

Anxiety disorder	GJH (%)	Controls (%)	OR (95% CI)	P
Separation anxiety	29.9	9.2	4.49 (2.39-8.43)	<.001
Social phobia	32.1	11.5	4.32 (2.40-7.75)	<.001
Panic/agoraphobia	11.2	3.5	3.46 (1.30-9.21)	.008
Generalized anxiety	10.3	3.8	2.87 (1.10-7.47)	.02
OCD	6.6	5.3	1.03 (0.42-2.57)	.94
Specific phobia	7.1	6.2	1.13 (0.47-2.74)	.78
ADHD symptoms	4.4	3.1	2.08 (0.54-7.97)	.26

Discussion

This large, well-controlled study found strong and statistically significant associations between GJH and multiple anxiety disorders in children. Notably, separation anxiety, social phobia, panic disorder/agoraphobia, and GAD were all more common in hypermobile children compared with non-hypermobile peers.

These findings are consistent with earlier work by Bulbena et al ⁷ who identified anxiety, particularly panic and agoraphobia, as being markedly elevated in hypermobile adults. ⁹ de Vries et al ¹² and Eccles et al ¹⁰ later expanded these findings to adolescents, showing that GJH at age 14 predicted anxiety and depression by age 18 years. Our study extends this relationship downward in age, indicating that even younger children with GJH may be at elevated risk.

Several potential mechanisms may explain these associations. One hypothesis is that autonomic nervous system dysregulation in hypermobile individuals predisposes them to heightened physiological arousal and anxiety. ¹² Another is interoceptive sensitivity, where children with GJH may misinterpret normal bodily sensations as threatening, leading to increased anxiety. Moreover, central sensitization and shared genetic factors affecting both connective tissue and neural development have been proposed.^5,7

Clinically, these findings suggest that pediatricians and school health providers should be alert to the mental health status of children presenting with hypermobility, even when no pain or fatigue is reported. Screening tools like the SCAS could be easily integrated into school-based health checks or primary care visits.

Strengths and limitations

Strengths of our research are that we used a large sample. Also, 3 examiners separately examined the students. The Beighton score used to diagnose GJH in children is valid and accepted. The limitation of this study was that we only used a questionnaire to diagnose anxiety disorders and did not confirm it with other methods.

Conclusion

Children with GJH are significantly more likely to exhibit specific anxiety disorders, particularly separation anxiety, social phobia, panic disorder, and GAD. Given the simplicity of GJH diagnosis via the Beighton scoring, routine psychological screening in this population should be considered in school health systems and pediatric clinics. Early detection and intervention may improve developmental trajectories and reduce long-term psychiatric morbidity.

Future longitudinal studies are needed to clarify the causal direction of these associations and to explore whether treating anxiety in GJH patients can influence physical symptoms and functional outcomes.