Joint hypermobility syndromes: The pathophysiologic role of tenascin‐X gene defects

Zweers, Manon C.; Hakim, Alan J.; Grahame, Rodney; Schalkwijk, Joost

doi:10.1002/art.20488

Cited by 81 publications

(58 citation statements)

References 75 publications

(65 reference statements)

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“…Mutations in COL3A1 result in vascular-type EDS. Recently, Zweers et al (22)(23)(24) suggested that a Tenascin-X mutation could well be a candidate for joint hypermobility. Those authors believe that complete or partial deficiency (haploinsufficiency) of Tenascin-X can result in 2 distinct hereditary CTDs in which hypermobility is present, indicating that Tenascin-X has an essential role in the mechanical properties of skin, ligaments, and tendons (23).…”

Section: Discussionmentioning

confidence: 99%

Clinical study of hereditary disorders of connective tissues in a Chilean population

Bravo¹,

Wolff²

2006

Arthritis & Rheumatism

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Objective. To demonstrate the high frequency and lack of diagnosis of joint hypermobility syndrome (JHS) and the seriousness of vascular Ehlers-Danlos syndrome (VEDS).Methods. Two hundred forty-nine Chilean patients with hereditary disorders of the connective tissues (CTDs) and 64 control subjects were evaluated for the diagnoses of JHS and VEDS using the validated Brighton criteria, as compared with the traditional Beighton score. In addition, the presence of blue sclera was determined, with the degree of intensity graded as mild, moderate, or marked.Results. The frequency of hereditary CTDs was 35%, with diagnoses of JHS in 92.4% of subjects, VEDS in 7.2%, and osteogenesis imperfecta in 0.4%. The Beighton score proved to be insufficient for the diagnosis of JHS (35% of subjects had a negative score), whereas the Brighton criteria yielded positive findings (a diagnosis of JHS) in 39% of control subjects. Blue sclera was frequent, being identified in 97% of JHS patients and 94% of VEDS patients. Moderate osteopenia/osteoporosis was observed in 50% of patients with VEDS and 26% of those with JHS. Dysautonomia, dyslipidemia, and scoliosis were more frequent in VEDS patients than in JHS patients. The typical JHS facial appearance and the "hand holding the head sign" were identified. Raynaud's phenomenon was extremely rare in JHS patients (2%). Ruptured uterus and cerebral aneurysm occurred in 12% and 6% of VEDS patients, respectively. Spontaneous pneumothorax was more frequent in VEDS patients (11%) than in JHS patients (0.9%).Conclusion. JHS is very frequent but usually undiagnosed. The Beighton score is an insufficient method for JHS diagnosis. We recommend that physicians learn to recognize the typical facial features of JHS and be able to identify blue sclera. We also propose that validated hypermobility criteria be routinely used. Further research is needed to determine why the prevalence of JHS is so high in Chile.Hippocrates first described hypermobile joints 2,400 years ago, but the condition of joint hypermobility was not described as a medical problem until 1967, by Kirk et al (1). Although many people have hypermobile joints, the general public as well as many physicians consider hypermobility to be a curiosity rather than a potentially serious medical problem (2,3). The prevalence of hypermobility is difficult to evaluate because it varies with age, sex, and ethnic background and because multiple criteria are being used. It is more frequent in female subjects and children, is more frequent in Asian than in black populations, and is more frequent in both Asian and black populations than in whites. It is generally agreed that it exists in ϳ10% of individuals in Western populations (4) and up to 25% in Iraqis (5). Most cases of joint hypermobility are pauciarticular rather than generalized, which makes the diagnosis more difficult. Because of this, many people are unaware of having lax joints (6). In spite of this laxity in the joints, most people with hypermobility do not experience joint or musculoskelet...

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Section: Discussionmentioning

confidence: 99%

Clinical study of hereditary disorders of connective tissues in a Chilean population

Bravo¹,

Wolff²

2006

Arthritis & Rheumatism

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“…Until recently, the syndrome has been associated with either dominant negative genetic defects in collagen structure (collagen types I, III, V) or recessive deficiencies in collagenprocessing enzymes such as lysyl hydroxylase and procollagen peptidase (45). The association of tenascin-X deficiency with Ehler-Danlos Syndrome, in addition to demonstrating the first clinical relevance for a tenascin family protein, has established for the first time that causative gene defects for this and similar syndromes can extend beyond those directly related to the collagens and their metabolism (45,46). The tenascin-X-associated form is transmitted in recessive fashion with collagen fibrils that have subtle morphologic alterations, such as lower degrees of packing density and co-alignment, but otherwise appear normal.…”

Section: Minireview: Tenascins 26642mentioning

confidence: 99%

Meet the Tenascins: Multifunctional and Mysterious

Hsia

Schwarzbauer

2005

Journal of Biological Chemistry

149

112

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“…6 Mutations in different collagens and collagen-modifying enzymes have been recognized for all sub-types of EDS with the exception of type III hypermobility-type EDS. 7 The collagens represent a large family of structurally related extracellular matrix proteins essential for development, cell attachment, platelet aggregation and for providing tensile strength to the connective tissues in bone, skin, ligaments and tendons, and blood vessels. 8 Loss of the elasticity and strength of collagen in EDS presumably contributes to the structural failure in connective tissue of the various affected organ systems.…”

Section: Geneti Cs Of Periventricular Heterotopia Andmentioning

confidence: 99%

Periventricular Heterotopia: New Insights into Ehlers-Danlos Syndrome

Sheen¹,

Walsh²

2005

Clinical Medicine & Research

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Nature often employs similar mechanisms to complete similar tasks, thus the evolution of homologous proteins across various organ systems to perform similar but slightly different functions. In this respect, disorders attributed to specific genetic mutations, while initially thought to be restricted in function and purpose, may provide broad insight into general cellular and molecular mechanisms of development and maintenance. One such example can be seen in the brain malformation, periventricular heterotopia (PH), which is characterized by very specific nodules of neurons that line the lateral ventricles beneath the cerebral cortex. PH is seen as a disorder of neuronal migration and can be caused by mutations in filamin A (FLNA), which encodes an actin-binding protein that regulates the cytoskeleton and cell motility. Recent advances in our understanding of the genetic causes of PH suggest that mutations in this gene, however, are also associated with the connective tissue disorder, Ehlers-Danlos syndrome (EDS), in which affected individuals present with joint and skin hyperextensibility and vascular problems including aortic dissection, excessive bleeding and bruisability.While much still remains unknown regarding the mechanistic role of FLNA in giving rise to PH and EDS, a common cellular and molecular basis likely gives rise to these two seemingly unrelated clinical disorders.

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Joint hypermobility syndromes: The pathophysiologic role of tenascin‐X gene defects

Cited by 81 publications

References 75 publications

Clinical study of hereditary disorders of connective tissues in a Chilean population

Clinical study of hereditary disorders of connective tissues in a Chilean population

Meet the Tenascins: Multifunctional and Mysterious

Periventricular Heterotopia: New Insights into Ehlers-Danlos Syndrome

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