CTGT, Ehlers-Danlos Syndrome, Genes- COL5A1, COL5A2

Collect at NMCP only Mon-Thursday by 1200. 1134 Seq.; 1535 Del / Dup; 1536 Seq. & Del / Dup

1536

Ehlers-Danlos syndrome, type I / II (EDS I / II), COL5A1 & COL5A2

4 ml EDTA whole blood (purple top)

4 ml EDTA whole blood (purple top)

4°C

Ehlers-Danlos syndrome (EDS) is a connective tissue disorder composed of numerous subtypes with distinct genetic and clinical findings. In general, EDS is characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The classical type of EDS includes EDS I (MIM 130000) and EDS II (MIM 130010). They are autosomal dominantly inherited disorders, and considered the most common types of EDS. Findings in patients with EDS I (gravis type) include marked skin involvement (hyperextensibility, atrophic scars) generalized joint hypermobility and complications there of (dislocations, subluxations, pes planus), muscular hypotonia, and delayed motor development. Additional findings may include rupture of the aorta or bowel. Prematurity is also common. Findings in EDS II (mitis type) are similar to, but less severe than, EDS I. The skin is less involved and joint laxity may be confined to hands and feet. Prematurity is not a feature. The vascular type, EDS IV, (MIM 130050), represents the most severe form of the disorder. Patients frequently suffer rupture of the arteries and intestine. The vascular type is an autosomal dominant disorder caused by mutations in COL3A1. The kyphoscoliotic type, EDS VI (MIM 225400), is an autosomal recessive disorder. It is characterized by severe muscular hypotonia, kyphoscoliosis at birth, generalized joint laxity, scleral fragility, and rupture of the ocular globe. Additional findings include arterial rupture, osteopenia, marfanoid habitus, microcornea, easy bruising, and atrophic scars. EDS VI is biochemically characterized by a deficiency of collagen lysyl hydroxylase due to mutations in PLOD1. The arthrochalasic type, EDS VIIA and VIIB (MIM 130060), is caused by mutations leading to the skipping of exon 6 in either COL1A1 (EDS VIIA) or COL1A2 (EDS VIIB). Inheritance is autosomal dominant. The arthrochalasic type is characterized by severe generalized joint hypermobility with recurrent subluxations and congenital hip dislocation. Short stature due to kyphoscoliosis can occur. Muscular hypotonia is evident at birth. Patients may be affected by osteopenia and bone fractures similar to mild osteogenesis imperfecta. The spondylocheiro dysplastic form of Ehlers-Danlos syndrome (SCD-EDS; MIM 612350) is a recently described autosomal recessive EDS-like disorder mainly involving the spine and hands. It is characterized by moderate short stature, slender tapering fingers, thenar/hypothenar muscle atrophy, and finely wrinkled palms. Clinical findings also include protuberant eyes with blue sclera, hyperelastic thin skin with an easily visible venous pattern and bruisability, and hypermobility of small joints eventually resulting in contractures. Radiological findings include platyspondyly, osteopenia, small ileum, broadened metaphyses of elbows, wrists, knees, and interphalangeal joints, and flattened proximal femoral epiphyses with short wide femoral necks. SCD-EDS is caused by mutations in the solute carrier family 39 (zinc transporter), member 13 gene, SLC39A13. The zinc transporter is suspected to be localized to intracellular membranes. It is speculated that transporter mutations cause increased concentrations of zinc in the endoplasmic reticulum. Zinc then competes with iron in iron dependent hydroxylation reactions involving lysyl hydroxylase, prolyl 4- hydroxylase and prolyl 3-hydroxylase. Consequently, collagens are underhydroxylated, and cross linking required for stability is impaired.