Joint hypermobility syndrome is a condition in which a joint can move effortlessly beyond the normal limit of motion expected for that joint. This syndrome is affected by some factors including gender and tends to be ...Joint hypermobility syndrome is a condition in which a joint can move effortlessly beyond the normal limit of motion expected for that joint. This syndrome is affected by some factors including gender and tends to be inherited. It may cause some symptoms such as pain in an individual’s synovial joints. The objective of the current study was to compare the energy loss of connective tissues between joints with and without hypermobility. A differential equation model, namely the Kelvin-Voigt model, was used for the energy loss analysis. The results show the difference in energy loss for the tissues attached to joints with and without joint hypermobility. As the stiffness of the connective tissue decreases, the energy loss increases. Muscle activity about the ankle was measured via electromyography during simple functional tasks, and the recorded data were used to correlate with the theoretical analysis of the energy loss. The result would shed light on the pathology analysis of the symptoms such as the cause of pain.展开更多
<strong>Background:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">Pilates has been shown to be an effective interventi...<strong>Background:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">Pilates has been shown to be an effective intervention for adults with musculoskeletal conditions with only a few examples available in the li</span><span style="font-family:Verdana;">terature for children. As musculoskeletal pain is a major symptom expe</span><span style="font-family:Verdana;">rienced by children with Hypermobility Spectrum Disorder (HSD), they may benefit from practicing Pilates to improve postural alignment, strength and motor control to effectively distribute movement load and decrease adverse load through involved joints. </span><b><span style="font-family:Verdana;">Method:</span></b><span style="font-family:Verdana;"> This study aims to evaluate the impact of a Physiotherapy-led Pilates intervention on school aged children with HSD and the benefits of this approach on pain, physical function and quality of life when delivered in a community-based model of care. A single-case experimental design (SCED) that incorporates a multiple baseline design will be used. Children with HSD, aged from 8 to 12 years, will commence concurrently in this study. Participants will undergo multiple assessments through all phases of the study which incorporates an A-B-A withdrawal design. The initial baseline period will be randomised from 5 to 7 weeks duration, then participants will enter the intervention period for 8 weeks followed by a withdrawal period of 5 weeks. The Physiotherapy-led Pilates intervention will consist of individual, 45 minute bi-weekly sessions, performed on both mat and the Pilates Reformer with an additional home program of mat exercises performed weekly. The study hypotheses are that children will show: 1) a decrease in pain;2) an increase in their physical function as measured by muscle strength, postural control, fatigue and physical activity levels;and 3) an improvement in their Health Related Quality of Life in the domains of physical, emotional, social and school functioning. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The findings will add specific responsiveness information to the scientific evidence for Physiotherapy-led Pilates for children with HSD.</span></span></span></span>展开更多
Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change add...Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.展开更多
Findings in 1656 patients referred for evaluation of Ehlers-Danlos syndrome, 710 evaluated systematically using novel history and physical forms, defined a characteristic clinical pattern termed arthritis-adrenaline d...Findings in 1656 patients referred for evaluation of Ehlers-Danlos syndrome, 710 evaluated systematically using novel history and physical forms, defined a characteristic clinical pattern termed arthritis-adrenaline disorder, a genus that provides immediate therapy while delineation of particular tissue laxity/dysautonomia species is underway. Preliminary diagnoses, clinical findings, and laboratory results were entered into an MS Excel? database with IRB approval and correlations or statistical significance analyzed using Excel? functions. Frequencies of 80 findings by history and 40 on physical were similar among EDS groups, females paralleling males with more total history (35 versus 23) and physical (18 versus 15) findings. Finding frequencies in joint-skeletal (6.2 of 15) and dysautonomia (11 of 20) subcategories were substantial regardless of age, EDS diagnosis, or referral source, the latter was shown by 6.4 and 13 average findings for cardiology, 5.3 and 8.3 for orthopedic referrals. Early affliction evidenced by history findings averaging 19.5 in those under 12 increased dramatically to 25 for teens and 32 for adults with plateauing at older ages arguing against degenerative disease. Frequent neuromuscular symptoms in females emphasize surrounding muscle support and protection of joint-connective tissue as a key factor in decreased male severity. The congruent clinical profile suggests operation of an articulo-autonomic dysplasia cycle where lax vessels and lower body pooling elicit sympathetic response, autonomic imbalance in turn affecting small nerve fibers and enhancing connective tissue laxity. Recognition of this arthritis-adrenalin disorder can guide management strategies while underlying causes are pursued, among them, physical therapy, exercise, and vitamin D to build muscle/bone strength;lower gluten/dairy and antihistamine protocols for low bowel motility/mast-cell activation;hydration, salt, and exercise for postural orthostatic tachycardia syndrome.展开更多
Ehlers-Danlos syndrome(EDS)is a heterogeneous group of connective tissue disorders comprised of several types.Classic EDS is an autosomal dominant disorder with stretchable skin,delayed wound healing with poor scarrin...Ehlers-Danlos syndrome(EDS)is a heterogeneous group of connective tissue disorders comprised of several types.Classic EDS is an autosomal dominant disorder with stretchable skin,delayed wound healing with poor scarring,joint hypermobility with subluxations or dislocations,easy bruisability,hernias,aneurysms and cardiac abnormalities.Advances in genomics technology using next-generation sequencing has led to the discovery of causative genes for connective tissue disorders,hereditary cardiomyopathies and cardiovascular diseases including several genes for connective tissue disorders.A 55 year-old male exhibited thin stretchable skin,atrophic scars,easy bruising,joint pain and dislocations requiring multiple knee surgeries and a Beighton hyperflexibility score of 6 out of 7.He was found to have a heterozygous missense COL5A1 gene variant involving exon 3 at nucleotide c:305T>A with an amino acid position change at p.lle102Asn consistent with classic EDS.He had a heart transplant at 43 years of age due to cardiac failure of unknown cause.This patient with classic EDS is brought to medical attention and should be of interest to cardiologists,heart transplant specialists and surgeons,particularly in individuals with unexplained cardiac failure and then diagnosed prior to surgical intervention to avoid poor wound healing,scarring and other tissue involvement(e.g.,vascular anomalies,blood pressure instability,aneurysms)as components of EDS.展开更多
The mind is embodied;thoughts and feelings interact with states of physiological arousal and physical integrity of the body.In this context,there is mounting evidence for an association between psychiatric presentatio...The mind is embodied;thoughts and feelings interact with states of physiological arousal and physical integrity of the body.In this context,there is mounting evidence for an association between psychiatric presentations and the expression variant connective tissue,commonly recognised as joint hypermobility.Joint hypermobility is common,frequently under-recognised,significantly impacts quality of life,and can exist in isolation or as the hallmark of hypermobility spectrum disorders(encompassing joint hypermobility syndrome and hypermobile Ehlers-Danlos syndrome).In this narrative review,we appraise the current evidence linking psychiatric disorders across the lifespan,beginning with the relatively well-established connection with anxiety,to hypermobility.We next consider emerging associations with affective illnesses,eating disorders,alongside less well researched links with personality disorders,substance misuse and psychosis.We then review related findings relevant to neurodevelopmental disorders and stress-sensitive medical conditions.With growing understanding of mind-body interactions,we discuss potential aetiopathogenetic contributions of dysautonomia,aberrant interoceptive processing,immune dysregulation and proprioceptive impairments in the context of psychosocial stressors and genetic predisposition.We examine clinical implications of these evolving findings,calling for increased awareness amongst healthcare professionals of the transdiagnostic nature of hypermobility and related disorders.A role for early screening and detection of hypermobility in those presenting with mental health and somatic symptoms is further highlighted,with a view to facilitate preventative approaches alongside longer-term holistic management strategies.Finally,suggestions are offered for directions of future scientific exploration which may be key to further delineating fundamental mind-body-brain interactions.展开更多
We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A 〉 T nucleotide transition in the TNXB gene causing...We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A 〉 T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classifed as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient’s symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome （EDS）. At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X defciency, but the variant identifed in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A 〉 T nucleotide transition in the TNXB gene may be classifed as disease-causing for EDS due to tenascin-X defciency.展开更多
Introduction: A new electromechanical instrument has been developed to measure relative dorsal mobility of the first ray in an objective and reliable way by simulating ground reaction forces during gait. This device e...Introduction: A new electromechanical instrument has been developed to measure relative dorsal mobility of the first ray in an objective and reliable way by simulating ground reaction forces during gait. This device equally applies a standardized, electronically controlled, and precise force under the first metatarsal head M1 as well as under the heads of the lesser metatarsals M2 to M5. The relative dorsal mobility between these two bearings is then measured. The purpose of this study is to assess the intra- and inter-examiners reliabilities of the measurements obtained with this device. Methods: The protocol included two examiners and 36 feet (18 volunteers with healthy feet and no history of forefoot disorders). A total of nine measurements were performed on each foot separated into three sets of three trials for the assessment of inter-rater and intra-rater reliability. For this purpose, the interclass correlation coefficient (ICC), the error of measurement (SEM) and the Bland and Altman (B&A) graphical analysis were computed. Results: Excellent ICC values (≥0.91) were obtained with the novel device for inter-rater and intra-rater reliability when using the FRRM calculation. The B&A analysis presented a bias between examiners of -0.25 mm ranging from -1.66 to 1.18 mm. Conclusion: This study demonstrated the capability of the developed device to reliably measure the relative dorsal mobility of the first ray of the foot. This is a promising first step for further studies to better understand, qualify and quantify first ray hypermobility.展开更多
Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of pa...Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of patients with Ehlers-Danlos syndrome have anxiety that meets criteria of generalized anxiety disorder, their clinical-DNA findings worth examining as biomarkers for patients with generalized anxiety. Method: Of the 1899 patients diagnosed with Ehlers-Danlos syndrome, 1261 were systematically evaluated for 80 history and 40 physical findings and separated into 826 who reported anxiety and 435 who did not. The most consistently reported or management-directing 60 of these clinical findings were, along with variations in genes relevant to these disorders, examined for association with anxiety. Results: Among the 30 anxiety- associated findings judged most predictive of Ehlers-Danlos syndrome in patients with anxiety were expected ones of adrenergic stimulation (difficulty concentrating-87% frequency and 1.26 anxiety/no anxiety ratio;chronic fatigue-84%, 1.17;sleep issues 69%, 1.52 that are criteria for generalized anxiety disorder) or of cholinergic suppression (e.g., frequent nausea 64%, 1.26). Less associated but more discriminating for underlying disease were those reflective of neuromuscular impact (e.g., chronic daily headaches 76%, 1.12);hypermobility (e.g., awareness of flexibility 72%, 1.03), or skin changes (e.g., elasticity around jaw 71%, 1.06). Anxiety-associated DNA variants included 54 of 88 in collagen type I/V/VII/IX genes, 14 of 16 in sodium channel SCN9A/10A/ 11A genes, 59 of 85 in POLG/MT-DNA genes, and 21 of 28 in profilaggrin- FLG genes that respectively impacted tissue laxity, sensory neural, autonomic-mitochondrial, and autonomic-inflammatory functions. Conclusion: Analysis of pathogenetic mechanisms in Ehlers-Danlos syndrome selected some 50 clinical-DNA findings useful for its diagnosis in those with generalized anxiety disorders.展开更多
Introduction:People are now presenting with chronic musculoskeletal pain at a younger age,and many of them fulfil criteria for fibromyalgia.We have recently shown a strong association between fibromyalgia symptoms and...Introduction:People are now presenting with chronic musculoskeletal pain at a younger age,and many of them fulfil criteria for fibromyalgia.We have recently shown a strong association between fibromyalgia symptoms and autistic traits in a self-selected community population,with the relationship mediated in part by the presence of hypermobility.Many respondents also described food sensitivities and intolerances.This study explores the relationships between food issues and fibromyalgia symptoms in this population.Methods:We adopted a nonexperimental,correlational design and collected data from a volunteer sample of 442 adults(aged 18–60)who completed online self-report questionnaires assessing each of fibromyalgia symptoms(ACR criteria),autistic traits(RAADS score)and hypermobility(Beighton’s test).Subjects were also asked to record any food sensitivities,allergies,or intolerances,along with their consequences.Correlation analyses and linear regressions were used to test the relationships between these features and each of fibromyalgia,autistic traits and hypermobility.We analysed the data with parametric and non-parametric techniques to assess the significance and power of relationships,and the potential mediating effect of food-related symptoms in the correlation between fibromyalgia features and autistic traits.Results:Our self-selected community population had a mean age of 24 years and was 77%female.The self-reported prevalence of fibromyalgia,autistic traits and hypermobility was 40%,65%and 44%respectively.Hypermobile individuals showed a high prevalence of autistic traits,reaching 79%among females and 88%among males.Half of all subjects reported food sensitivity and 31%reported food intolerance.The incidence of food-related symptoms was higher among subjects who met criteria for fibromyalgia than those who reported autistic traits or hypermobility.Food sensitivity and food intolerance were both more significantly associated with fibromyalgia(r=0.24,P>0.001 and r=0.38,P>0.001)than with autistic traits(r=0.172,P>0.01 and r=0.148,P>0.01).Discussion:This community study provides evidence for an association between features of fibromyalgia and reported food intolerance and sensitivity.Although self-selected,the findings in our predominantly young population suggest that gluten and lactose consumption may be associated with higher levels of musculoskeletal pain.The study population commonly reported that avoidance of gluten and/or lactose containing foods reduced symptoms.Dietary adjustment may merit further investigation as a therapeutic modality for some patients with fibromyalgia.展开更多
Objective: To investigate the incidence of hypermobility in infants at the age of three months. Method: Eighty-one healthy infants aged three months were examined using the Beighton score. The spine was excluded for p...Objective: To investigate the incidence of hypermobility in infants at the age of three months. Method: Eighty-one healthy infants aged three months were examined using the Beighton score. The spine was excluded for practical reasons;due to this the highest possible Beighton score for the participants in this study was 8. Also ankle dorsiflexion and the big toe were examined. Results: The mean score on the Beighton scale was 2.7;median was 2.0 and the range was 0 to 6. Almost half of the infants scored at least 4 on the Beighton scale. T test showed no gender difference. Neither was there any difference between right and left sides. Conclusions: Infants at the age of three months have high mobility in the distal joints, ankle dorsiflexion, thumb and little finger. It is rare to find hypermobility in elbows and knees at this age.展开更多
Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is most...Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type Ⅰ procollagen.In this study,we identified a Thai patient having OI type Ⅲ,EDS,brachydactyly,and dentinogenesis imperfecta.His dentition showed delayed eruption,early exfoliation,and severe malocclusion.For the first time,ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion,bonelike dentin,loss of dentinal tubules,and reduction in hardness and elasticity,suggesting severe developmental disturbance.These severe dental defects have never been reported in OI or EDS.Exome sequencing identified a novel de novo heterozygous glycine substitution,c.3296G>A,p.Gly1099Glu,in exon 49 of COL1A2.Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage.Notably,two of these three patients did not show hyperextensible joints and hypermobile skin,while our patient at the age of 5 years had not developed intracranial hemorrhage.Here,we demonstrate that the novel glycine substitution in the carboxyl region of alpha2(Ⅰ)collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects,expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.展开更多
文摘Joint hypermobility syndrome is a condition in which a joint can move effortlessly beyond the normal limit of motion expected for that joint. This syndrome is affected by some factors including gender and tends to be inherited. It may cause some symptoms such as pain in an individual’s synovial joints. The objective of the current study was to compare the energy loss of connective tissues between joints with and without hypermobility. A differential equation model, namely the Kelvin-Voigt model, was used for the energy loss analysis. The results show the difference in energy loss for the tissues attached to joints with and without joint hypermobility. As the stiffness of the connective tissue decreases, the energy loss increases. Muscle activity about the ankle was measured via electromyography during simple functional tasks, and the recorded data were used to correlate with the theoretical analysis of the energy loss. The result would shed light on the pathology analysis of the symptoms such as the cause of pain.
文摘<strong>Background:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">Pilates has been shown to be an effective intervention for adults with musculoskeletal conditions with only a few examples available in the li</span><span style="font-family:Verdana;">terature for children. As musculoskeletal pain is a major symptom expe</span><span style="font-family:Verdana;">rienced by children with Hypermobility Spectrum Disorder (HSD), they may benefit from practicing Pilates to improve postural alignment, strength and motor control to effectively distribute movement load and decrease adverse load through involved joints. </span><b><span style="font-family:Verdana;">Method:</span></b><span style="font-family:Verdana;"> This study aims to evaluate the impact of a Physiotherapy-led Pilates intervention on school aged children with HSD and the benefits of this approach on pain, physical function and quality of life when delivered in a community-based model of care. A single-case experimental design (SCED) that incorporates a multiple baseline design will be used. Children with HSD, aged from 8 to 12 years, will commence concurrently in this study. Participants will undergo multiple assessments through all phases of the study which incorporates an A-B-A withdrawal design. The initial baseline period will be randomised from 5 to 7 weeks duration, then participants will enter the intervention period for 8 weeks followed by a withdrawal period of 5 weeks. The Physiotherapy-led Pilates intervention will consist of individual, 45 minute bi-weekly sessions, performed on both mat and the Pilates Reformer with an additional home program of mat exercises performed weekly. The study hypotheses are that children will show: 1) a decrease in pain;2) an increase in their physical function as measured by muscle strength, postural control, fatigue and physical activity levels;and 3) an improvement in their Health Related Quality of Life in the domains of physical, emotional, social and school functioning. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The findings will add specific responsiveness information to the scientific evidence for Physiotherapy-led Pilates for children with HSD.</span></span></span></span>
文摘Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.
文摘Findings in 1656 patients referred for evaluation of Ehlers-Danlos syndrome, 710 evaluated systematically using novel history and physical forms, defined a characteristic clinical pattern termed arthritis-adrenaline disorder, a genus that provides immediate therapy while delineation of particular tissue laxity/dysautonomia species is underway. Preliminary diagnoses, clinical findings, and laboratory results were entered into an MS Excel? database with IRB approval and correlations or statistical significance analyzed using Excel? functions. Frequencies of 80 findings by history and 40 on physical were similar among EDS groups, females paralleling males with more total history (35 versus 23) and physical (18 versus 15) findings. Finding frequencies in joint-skeletal (6.2 of 15) and dysautonomia (11 of 20) subcategories were substantial regardless of age, EDS diagnosis, or referral source, the latter was shown by 6.4 and 13 average findings for cardiology, 5.3 and 8.3 for orthopedic referrals. Early affliction evidenced by history findings averaging 19.5 in those under 12 increased dramatically to 25 for teens and 32 for adults with plateauing at older ages arguing against degenerative disease. Frequent neuromuscular symptoms in females emphasize surrounding muscle support and protection of joint-connective tissue as a key factor in decreased male severity. The congruent clinical profile suggests operation of an articulo-autonomic dysplasia cycle where lax vessels and lower body pooling elicit sympathetic response, autonomic imbalance in turn affecting small nerve fibers and enhancing connective tissue laxity. Recognition of this arthritis-adrenalin disorder can guide management strategies while underlying causes are pursued, among them, physical therapy, exercise, and vitamin D to build muscle/bone strength;lower gluten/dairy and antihistamine protocols for low bowel motility/mast-cell activation;hydration, salt, and exercise for postural orthostatic tachycardia syndrome.
基金the National Institute of Child Health and Human Development,No.HD02528。
文摘Ehlers-Danlos syndrome(EDS)is a heterogeneous group of connective tissue disorders comprised of several types.Classic EDS is an autosomal dominant disorder with stretchable skin,delayed wound healing with poor scarring,joint hypermobility with subluxations or dislocations,easy bruisability,hernias,aneurysms and cardiac abnormalities.Advances in genomics technology using next-generation sequencing has led to the discovery of causative genes for connective tissue disorders,hereditary cardiomyopathies and cardiovascular diseases including several genes for connective tissue disorders.A 55 year-old male exhibited thin stretchable skin,atrophic scars,easy bruising,joint pain and dislocations requiring multiple knee surgeries and a Beighton hyperflexibility score of 6 out of 7.He was found to have a heterozygous missense COL5A1 gene variant involving exon 3 at nucleotide c:305T>A with an amino acid position change at p.lle102Asn consistent with classic EDS.He had a heart transplant at 43 years of age due to cardiac failure of unknown cause.This patient with classic EDS is brought to medical attention and should be of interest to cardiologists,heart transplant specialists and surgeons,particularly in individuals with unexplained cardiac failure and then diagnosed prior to surgical intervention to avoid poor wound healing,scarring and other tissue involvement(e.g.,vascular anomalies,blood pressure instability,aneurysms)as components of EDS.
文摘The mind is embodied;thoughts and feelings interact with states of physiological arousal and physical integrity of the body.In this context,there is mounting evidence for an association between psychiatric presentations and the expression variant connective tissue,commonly recognised as joint hypermobility.Joint hypermobility is common,frequently under-recognised,significantly impacts quality of life,and can exist in isolation or as the hallmark of hypermobility spectrum disorders(encompassing joint hypermobility syndrome and hypermobile Ehlers-Danlos syndrome).In this narrative review,we appraise the current evidence linking psychiatric disorders across the lifespan,beginning with the relatively well-established connection with anxiety,to hypermobility.We next consider emerging associations with affective illnesses,eating disorders,alongside less well researched links with personality disorders,substance misuse and psychosis.We then review related findings relevant to neurodevelopmental disorders and stress-sensitive medical conditions.With growing understanding of mind-body interactions,we discuss potential aetiopathogenetic contributions of dysautonomia,aberrant interoceptive processing,immune dysregulation and proprioceptive impairments in the context of psychosocial stressors and genetic predisposition.We examine clinical implications of these evolving findings,calling for increased awareness amongst healthcare professionals of the transdiagnostic nature of hypermobility and related disorders.A role for early screening and detection of hypermobility in those presenting with mental health and somatic symptoms is further highlighted,with a view to facilitate preventative approaches alongside longer-term holistic management strategies.Finally,suggestions are offered for directions of future scientific exploration which may be key to further delineating fundamental mind-body-brain interactions.
基金Supported by The National Institute of Child Health and Human Development(NICHD),No.HD02528
文摘We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A 〉 T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classifed as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient’s symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome （EDS）. At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X defciency, but the variant identifed in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A 〉 T nucleotide transition in the TNXB gene may be classifed as disease-causing for EDS due to tenascin-X defciency.
文摘Introduction: A new electromechanical instrument has been developed to measure relative dorsal mobility of the first ray in an objective and reliable way by simulating ground reaction forces during gait. This device equally applies a standardized, electronically controlled, and precise force under the first metatarsal head M1 as well as under the heads of the lesser metatarsals M2 to M5. The relative dorsal mobility between these two bearings is then measured. The purpose of this study is to assess the intra- and inter-examiners reliabilities of the measurements obtained with this device. Methods: The protocol included two examiners and 36 feet (18 volunteers with healthy feet and no history of forefoot disorders). A total of nine measurements were performed on each foot separated into three sets of three trials for the assessment of inter-rater and intra-rater reliability. For this purpose, the interclass correlation coefficient (ICC), the error of measurement (SEM) and the Bland and Altman (B&A) graphical analysis were computed. Results: Excellent ICC values (≥0.91) were obtained with the novel device for inter-rater and intra-rater reliability when using the FRRM calculation. The B&A analysis presented a bias between examiners of -0.25 mm ranging from -1.66 to 1.18 mm. Conclusion: This study demonstrated the capability of the developed device to reliably measure the relative dorsal mobility of the first ray of the foot. This is a promising first step for further studies to better understand, qualify and quantify first ray hypermobility.
文摘Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of patients with Ehlers-Danlos syndrome have anxiety that meets criteria of generalized anxiety disorder, their clinical-DNA findings worth examining as biomarkers for patients with generalized anxiety. Method: Of the 1899 patients diagnosed with Ehlers-Danlos syndrome, 1261 were systematically evaluated for 80 history and 40 physical findings and separated into 826 who reported anxiety and 435 who did not. The most consistently reported or management-directing 60 of these clinical findings were, along with variations in genes relevant to these disorders, examined for association with anxiety. Results: Among the 30 anxiety- associated findings judged most predictive of Ehlers-Danlos syndrome in patients with anxiety were expected ones of adrenergic stimulation (difficulty concentrating-87% frequency and 1.26 anxiety/no anxiety ratio;chronic fatigue-84%, 1.17;sleep issues 69%, 1.52 that are criteria for generalized anxiety disorder) or of cholinergic suppression (e.g., frequent nausea 64%, 1.26). Less associated but more discriminating for underlying disease were those reflective of neuromuscular impact (e.g., chronic daily headaches 76%, 1.12);hypermobility (e.g., awareness of flexibility 72%, 1.03), or skin changes (e.g., elasticity around jaw 71%, 1.06). Anxiety-associated DNA variants included 54 of 88 in collagen type I/V/VII/IX genes, 14 of 16 in sodium channel SCN9A/10A/ 11A genes, 59 of 85 in POLG/MT-DNA genes, and 21 of 28 in profilaggrin- FLG genes that respectively impacted tissue laxity, sensory neural, autonomic-mitochondrial, and autonomic-inflammatory functions. Conclusion: Analysis of pathogenetic mechanisms in Ehlers-Danlos syndrome selected some 50 clinical-DNA findings useful for its diagnosis in those with generalized anxiety disorders.
文摘Introduction:People are now presenting with chronic musculoskeletal pain at a younger age,and many of them fulfil criteria for fibromyalgia.We have recently shown a strong association between fibromyalgia symptoms and autistic traits in a self-selected community population,with the relationship mediated in part by the presence of hypermobility.Many respondents also described food sensitivities and intolerances.This study explores the relationships between food issues and fibromyalgia symptoms in this population.Methods:We adopted a nonexperimental,correlational design and collected data from a volunteer sample of 442 adults(aged 18–60)who completed online self-report questionnaires assessing each of fibromyalgia symptoms(ACR criteria),autistic traits(RAADS score)and hypermobility(Beighton’s test).Subjects were also asked to record any food sensitivities,allergies,or intolerances,along with their consequences.Correlation analyses and linear regressions were used to test the relationships between these features and each of fibromyalgia,autistic traits and hypermobility.We analysed the data with parametric and non-parametric techniques to assess the significance and power of relationships,and the potential mediating effect of food-related symptoms in the correlation between fibromyalgia features and autistic traits.Results:Our self-selected community population had a mean age of 24 years and was 77%female.The self-reported prevalence of fibromyalgia,autistic traits and hypermobility was 40%,65%and 44%respectively.Hypermobile individuals showed a high prevalence of autistic traits,reaching 79%among females and 88%among males.Half of all subjects reported food sensitivity and 31%reported food intolerance.The incidence of food-related symptoms was higher among subjects who met criteria for fibromyalgia than those who reported autistic traits or hypermobility.Food sensitivity and food intolerance were both more significantly associated with fibromyalgia(r=0.24,P>0.001 and r=0.38,P>0.001)than with autistic traits(r=0.172,P>0.01 and r=0.148,P>0.01).Discussion:This community study provides evidence for an association between features of fibromyalgia and reported food intolerance and sensitivity.Although self-selected,the findings in our predominantly young population suggest that gluten and lactose consumption may be associated with higher levels of musculoskeletal pain.The study population commonly reported that avoidance of gluten and/or lactose containing foods reduced symptoms.Dietary adjustment may merit further investigation as a therapeutic modality for some patients with fibromyalgia.
文摘Objective: To investigate the incidence of hypermobility in infants at the age of three months. Method: Eighty-one healthy infants aged three months were examined using the Beighton score. The spine was excluded for practical reasons;due to this the highest possible Beighton score for the participants in this study was 8. Also ankle dorsiflexion and the big toe were examined. Results: The mean score on the Beighton scale was 2.7;median was 2.0 and the range was 0 to 6. Almost half of the infants scored at least 4 on the Beighton scale. T test showed no gender difference. Neither was there any difference between right and left sides. Conclusions: Infants at the age of three months have high mobility in the distal joints, ankle dorsiflexion, thumb and little finger. It is rare to find hypermobility in elbows and knees at this age.
基金supported by the 90th Anniversary of Chulalongkorn University,Rachadapisek Sompote FundFaculty of Dentistry(DFR62003),Chulalongkorn University+3 种基金Chulalongkorn Academic Advancement Into Its 2nd Century ProjectNewton FundThailand Research Fund(RSA6280001,DPG6180001)supported by Ratchadapisek Somphot Fund for Postdoctoral Fellowship,Chulalongkorn University,Thailand。
文摘Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type Ⅰ procollagen.In this study,we identified a Thai patient having OI type Ⅲ,EDS,brachydactyly,and dentinogenesis imperfecta.His dentition showed delayed eruption,early exfoliation,and severe malocclusion.For the first time,ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion,bonelike dentin,loss of dentinal tubules,and reduction in hardness and elasticity,suggesting severe developmental disturbance.These severe dental defects have never been reported in OI or EDS.Exome sequencing identified a novel de novo heterozygous glycine substitution,c.3296G>A,p.Gly1099Glu,in exon 49 of COL1A2.Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage.Notably,two of these three patients did not show hyperextensible joints and hypermobile skin,while our patient at the age of 5 years had not developed intracranial hemorrhage.Here,we demonstrate that the novel glycine substitution in the carboxyl region of alpha2(Ⅰ)collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects,expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.
