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Ehlers-Danlos syndrome (EDS) represents a heterogeneous group of generalized connective tissue disorders. The various forms of EDS all result from defects in collagen synthesis and/or processing. Collagen is the most abundant protein in the body and serves as a major building block of the extracellular matrix. Collagens are proteins that all contain three chains wound in a triple helix. There are over 30 collagen genes dispersed throughout the genome and the protein products combine to form more than 20 different types of collagen. The major manifestations of EDS are skin fragility and hyperextensibility and joint hypermobility. To date, mutations in 8 genes involved in collagen synthesis or processing have been identified as causing the EDS phenotypes.
EDS types I and II are referred to as classical EDS.
Type I (gravis; also called the classic form) is the result of mutations in the collagen genes COL5A1 and COL5A2 and is inherited in an autosomal dominant manner. The characteristic clinical features of type I EDS are soft, velvety, and hyperextensible skin and easy bruising. The joints are quite hypermobile. Many patients with type I EDS have mitral valve prolapse. Trauma to the skin usually results in large gaping wounds that bleed less than expected. Repeated trauma to the knees, elbows and shins leads to pigmented scarring. In addition, the skin develops thin "cigarette-paper" scars as a result of trauma. OMIM Link
Type II (mitis) is inherited in autosomal dominant fashion (rare events of autosomal recessive) and is the result of mutations in COL5A1. Because the mutations that cause type II are in the same gene that cause type I the symptoms are similar to those of type I but less severe. OMIM Link
Type III (familial hypermobility) is inherited in autosomal dominant fashion and is the result of mutations in the COL1A2 gene with rare occasions of COL3A1 mutations. Type III is characterized by marked hypermobility of both the large and small joints. The skin is soft but doesn't scar like in type I. OMIM Link
Type IV is the arterial type of EDS (also referred to as the vascular form). It is inherited in autosomal dominant fashion and is the result of mutations in the COL3A1 genes. The mutations alter the synthesis, structure and secretion of type III collagen. The characteristic features of this form of EDS are thin, translucent skin with visible veins which causes marked bruising. Patients with type IV are subject to arterial, uterine and bowel rupture. OMIM Link
Type V is an X-linked disorder with symptoms similar to those of type II. The gene defect(s) in type V is not yet known. OMIM Link
Type VI is the ocular type of EDS (also referred to as the kyphoscoliosis form). It is inherited in an autosomal recessive manner and results from deficiencies in lysyl hydroxylase due to mutations in the procollagen-lysine 1,2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene. Patients have ocular fragility in addition to soft, velvety, hyperextensible skin and hypermobile joints. OMIM Link
Type VII comprises three distinct forms. Forms A and B are the arthrochalasis types (abnormal relaxation or flacidity of the joints) and C is the dermatosparaxis type (loss of skin strength and tearing). Type VIIA results from mutations in the COL1A1 gene that eliminates the N-proteinase cleavage site, type VIIB from mutations in the COL1A2 gene that eliminates the N-proteinase cleavage site and type VIIC that results from deficiencies in procollagen N-proteinase activity. OMIM Link for AR form
Type VIII is referred to as the periodontal type because of the generalized periodontitis. Skin anomalies in type VIII are similar to those found in EDS type II. The gene defect(s) in type VIII is not yet known. OMIM Link
Type IX is no longer considered a form of EDS and is now identified as X-linked cutis laxa or occipital horn syndrome.
Type X is similar in phenotype to EDS type II but is not due to a defective collagen. The cause of type X are defects in fibronectin. Fibronectins are a family of related adhesive glycoproteins. Fibronectins are important in connective tissue, where they cross-link to collagen. Type X EDS also has an associated platelet dysfunction due to the fibronectin abnormality. OMIM Link
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