Search

Joint hypermobility is a common, mostly benign, finding in the general population. In a subset of individuals, however, it causes a range of clinical problems, mainly affecting the musculoskeletal system. Joint hypermobility often appears as a familial trait and is shared by several heritable connective tissue disorders, including the hypermobility subtype of the Ehlers-Danlos syndrome (EDS-HT) or benign joint hypermobility syndrome (BJHS). These hereditary conditions provide unique models for the study of the genetic basis of joint hypermobility. Nevertheless, these studies are largely hampered by the great variability in clinical presentation and the often vague mode of inheritance in many families. Here, we performed a genome-wide linkage scan in a unique three-generation family with an autosomal dominant EDS-HT phenotype and identified a linkage interval on chromosome 8p22-8p21.1, with a maximum two-point LOD score of 4.73. Subsequent whole exome sequencing revealed the presence of a unique missense variant in the LZTS1 gene, located within the candidate region. Subsequent analysis of 230 EDS-HT/BJHS patients resulted in the identification of three additional rare variants. This is the first reported genome-wide linkage analysis in an EDS-HT family, thereby providing an opportunity to identify a new disease gene for this condition. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to investigate functional impairment and the impact of pain in patients with Ehlers-Danlos syndrome, hypermobility type (EDS-HT), and to compare the burden of disease with that in women with fibromyalgia (FM) and rheumatoid arthritis (RA). Methods A total of 206 female patients were compared (72 with EDS-HT, 69 with FM, and 65 with RA). Functional impairment was assessed with the Sickness Impact Profile (SIP), and the psychosocial impact of chronic pain was quantified with the Multidimensional Pain Inventory (MPI). Data on symptoms were collected. Results SIP results showed clinically relevant health-related dysfunction in all groups. Significantly poorer physical, psychosocial, and overall function was found in the EDS-HT group compared with the RA group. In comparison with the FM group, the EDS-HT group reported similar physical and overall function, but better psychosocial function. T scores from the MPI revealed significantly higher levels of pain severity and life interference due to pain, and a lower level of perceived life control, in the EDS-HT group compared to the RA group. In contrast, the EDS-HT group showed significantly lower levels of pain severity, life interference, and affective distress in comparison with the FM group. Social support for help in coping with pain was similar between the 3 groups. Conclusion EDS-HT is associated with a consistent burden of disease, similar to that of FM and worse than that of RA, as well as a broad impact of chronic pain on daily life, which needs to be addressed in the health care system. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the effectiveness of celiprolol to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome. The multicentre, randomised, open trial involved patients from eight centres in France and one centre in Belgium. The researchers found that celiprolol has the potential as a treatment option for patients with vascular Ehlers-Danlos syndrome.

Background: Aortic root dilation, dissection and rupture are major clinical problems in Marfan syndrome (MFS). Although β-blockers remain the standard of preventive treatment, preliminary results from animal studies and a selected group of severely affected MFS children show significant benefit from treatment with losartan, an angiotensin II receptor blocker with TGF-β inhibiting potential. Large-scale human trials are now needed to confirm these results. This trial aims to evaluate the combined effect of both drugs., Methods: We are conducting a prospective randomized placebo controlled double blind phase III study aiming to include 174 MFS patients (age ≥ 10 years and z-score ≥ 2). Patients already taking β-blockers are randomized for weight-adjusted treatment with losartan versus placebo. The primary endpoint is decrease in aortic root growth rate. Secondary endpoints are aortic dissection/surgery, progression of aortic/mitral regurgitation, arterial stiffness, left ventricular systolic/diastolic function, quality of life and genetic modifiers. Echocardiography, vascular echo-Doppler and quality of life assessment will be performed at baseline and at 6-monthly follow-ups for 3 years. MRI evaluation will be performed at baseline and at the end of the trial., Conclusion: This trial will study new therapeutic strategies for the prevention of serious cardiovascular complications in MFS. The uniqueness in our trial is that the additive effect of losartan and β-blocker will be evaluated in a large spectrum of disease severity. A combination of ultrasound and MRI will allow detailed evaluation of anatomic and functional properties of the aorta and left ventricle., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Osteogenesis Imperfecta (OI) is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of life as a conductive hearing loss, frequently evolving to mixed hearing loss thereafter. A minority of patients develop pure sensorineural hearing loss. The interindividual variability in the audiological characteristics of the hearing loss is unexplained., Methods: With the purpose of evaluating inter- and intrafamilial variability, hearing was thorougly examined in 184 OI patients (type I: 154; type III: 4; type IV: 26), aged 3-89 years, with a mutation in either COL1A1 or COL1A2 and originating from 89 different families. Due to the adult onset of hearing loss in OI, correlations between the presence and/or characteristics of the hearing loss and the underlying mutation were investigated in a subsample of 114 OI patients from 64 different families who were older than 40 years of age or had developed hearing loss before the age of 40., Results: Hearing loss was diagnosed in 48.4% of the total sample of OI ears with increasing prevalence in the older age groups. The predominant type was a mixed hearing loss (27.5%). A minority presented a pure conductive (8.4%) or pure sensorineural (12.5%) loss. In the subsample of 114 OI subjects, no association was found between the nature of the mutation in COL1A1 or COL1A2 genes and the occurrence, type or severity of hearing loss. Relatives originating from the same family differed in audiological features, which may partially be attributed to their dissimilar age., Conclusions: Our study confirms that hearing loss in OI shows a strong intrafamilial variability. Additional modifications in other genes are assumed to be responsible for the expression of hearing loss in OI.

Objective: To investigate balance, gait, falls, and fear of falling in patients with the hypermobility type of Ehlers-Danlos syndrome (EDS-HT)., Methods: Twenty-two women with EDS-HT and 22 sex- and age-matched healthy control subjects participated in the study. Each subject performed the modified Clinical Test of Sensory Interaction on Balance (mCTSIB) and the Tandem Stance test (TS) on an AccuGait force platform to assess balance by center of pressure-based postural sway measures. The GAITRite walkway system was used to record spatial-temporal gait variables during 3 walking conditions (single task, cognitive task, and functional task). Data about fall frequency and circumstances were collected by retrospective recall, and fear of falling was assessed by the modified Falls Efficacy Scale., Results: Compared with healthy subjects, EDS-HT subjects showed significantly impaired balance, reflected by increased sway velocity, mediolateral and anteroposterior sway excursion, and sway area during mCTSIB and TS. Gait velocity, step length, and stride length were significantly smaller during all walking conditions, and a significant dual-task-related decrement was found for gait velocity, step and stride length, and cadence in the EDS-HT subjects compared to the control group. Ninety-five percent of the patients fell during the past year, and some fear of falling was measured., Conclusion: To our knowledge, this study is the first to establish that EDS-HT is associated with balance and gait impairments, increased fall frequency, and poorer balance confidence, implying a decrease in the safety of standing in everyday life situations. Whether these deficits can be improved by appropriate exercise programs needs to be addressed in future research., (Copyright © 2011 by the American College of Rheumatology.)