Ehlers-Danlos syndrome

Ehlers-Danlos syndrome (Cutis hyperelastic) is a group of inherited disorders of connective tissue, caused by an error in the synthesis of collagen (a protein) in connective tissue. Collagen in the connective tissue with the tissue to resist deformation (low elasticity). The skin, muscles, ligaments, blood vessels and internal organs, collagen plays an important and with reduced elasticity, collagen abnormally high, the results of pathology. Depending on the individuals can change the severity of the syndrome varies from mild to fatal. There is no cure and treatment is symptomatic, including close monitoring of the cardiovascular system.

Pathophysiology

Ehlers-Danlos syndrome is a heterogeneous group of inherited disorders of connective tissue characterized by joint hypermobility, skin fragility and laxity. Failure of collagen was only 6 of 11 types of Ehlers-Danlos syndrome identified. Type IV is a small amount of collagen type III classified. Type V and VI are characterized by deficiencies in the hydroxylase and lysyl oxidase, a major modification enzyme in the posttranslational biosynthesis of collagen. Type VII deficiency in amino-terminal procollagen peptidase. Type IX has an unusual copper metabolism. X-Type is not functional plasma fibronectin.

Ehlers-Danlos syndrome type I and II, is the classic version, the identification of the molecular structure in most of those affected are difficult. It may involve mutations causing the COL5A1, COL5A2, and tenascin X genes and should be implicit in the COL1A2 gene. However, in most families with autosomal dominant Ehlers-Danlos disease appears to be linked loci COL5A1 and COL5A2 genes included. Even if half of the mutations cause Ehlers-Danlos syndrome type I and II are capable of COL5A1 gene, a significant proportion of mutations that reduce mutant mRNA due to nonsense-mediated mRNA decay.

Bouma et al evaluated 3 generations in a family with Ehlers-Danlos syndrome type II, the lack of a genome (-2) → G substitution in exon-14 splice acceptor site. The electronic transmission of images of type I collagen fibers in the skin biopsy, has a diameter fibrils heterogeneous object was higher than that of a control sample. The proband was found that a greater percentage of fibers have fibrils and occasional large and small, with a configuration of cauliflower were observed.

Wenstrup and staff identified haploinsufficiency of the COL5A1 gene coding for proalpha1 (V) chain of collagen type V in the classic form of Ehlers-Danlos syndrome. Eight of 28 patients with Ehlers-Danlos syndrome classic were heterozygous for the polymorphism of COL5A1 expression is complete or nearly complete loss of expression of one COL5A1 allele. A third of people with Ehlers-Danlos syndrome classics were COL5A1 mutations, which are haploinsufficiency. These results indicate that requires the formation of normal heterotypic collagen fibrils that contain types I, III, V and the expression of both COL5A1 collagen alleles.

Autosomal recessive type VI Ehlers-Danlos syndrome, also known as kyphoscoliotic type is characterized by neonatal kyphoscoliosis, generalized joint hypermobility, skin fragility, and severe muscle hypotonia at birth. Biochemical, such as a lack of lysyl hydroxylase (LH), the enzyme lysine residues of collagen specific hydroxylysine hydroxyl molecule with 2 important functions and formal. The residues are the sites linking to glucosylgalactose galactose, and act as a precursor to the networking process, collagen is its tensile strength.

More than 20 mutations in the gene for this deficiency and clinical LH1 Ehlers-Danlos syndrome type VI LH has been identified. Yeowell and Walker identified 2 of these mutations in at least 5 unrelated patients: (1) a large overlap of exons 10-16, resulting from homologous recombination of intronic Alu sequences, and (2) a nonsense mutation, Y511X in exon 14 of gene LH1. The two mutations appear to come from a single ancestor gene.

Tenascin-X is a main protein of the extracellular matrix, resulting in lack of a recessive form clinically different syndrome.5 then factors other than collagen or collagen-processing enzymes can cause this syndrome. This module just described may be associated with additional anomalies.

A case with perforation of the colon in a young girl with a fatal outcome, a new mutation in the COL3A1 gene are linked. Crystal structure of human type III in the structure of G991-G1032 cystine knot, both 7 / 2 and 10 / 3 symmetries.

A novel point mutation was found in the vascular type of Ehlers-Danlos syndrome. The mutation is in second position of exon 24 of COL3A1.
The healing of wounds is a typical characteristic of Ehlers-Danlos syndrome, probably a defect in fibroblasts. Healing can be obtained by exogenous type V collagen.
Ehlers-Danlos syndrome in pediatric patients has been shown that defects in 3 genes of glutathione S-transferase family (GSTM1, GSTT1, GSTP1). This leads to the formation of reactive oxygen species. Reduced activity of beta4-galactosyltransferase 7 (beta4GalT-7) is associated with the progeriform Ehlers-Danlos syndrome.