summary Ehlers-Danlos Syndrome is a congenital connective tissue disorder most commonly caused by a variety of mutation in collagen forming genes. Patients present with joint hypermobility, generalized ligamentous laxity, scoliosis, fragile skin, and cardiovascular abnormalities. Diagnosis is made by collagen typing in a skin biopsy. Treatment is usually physical therapy, orthotics, and supportive measures for pain. Surgical management is indicated for progressive scoliosis or progressive joint pain not responsive to non-operative management. Etiology Genetics COL5A1 or COL5A2 mutation in 40-50% gene for type V collagen login to view 1 more bullet less common mutations identified below Associated conditions Connective tissue disorder characterized by hyperelastic/fragile skin joint hypermobility and dislocation generalized ligamentous laxity poor wound healing early onset arthritis additional features login to view 10 more bullets Classification Berlin Classification (1988) - revised Types I - XI exist Types II and III - most common and least disabling Villefranche Classification (1998) Villefranche Classification New name Features Former name Classical Autosomal dominant Hyperextensible skin, widened atrophic scars, joint hypermobility COL5A1 or COL5A2 mutation; type V collagen (co-expressed with type I collagen) Type I (gravis), Type II (mitis) Hypermobile Autosomal dominant Large and small joint hypermobility, recurring joint subluxations/dislocations, velvety soft skin, chronic pain, scoliosis Unknown mutation Type III Vascular Autosomal dominant Translucent skin, arterial/intestinal/uterine fragility and spontaneous rupture, extensive bruising COL3A1 mutation; abnormal type III collagen Type IV Kyphoscoliosis Autosomal recessive Severe hypotonia at birth, generalized joint laxity, progressive infantile scoliosis, scleral fragility may lead to globe rupture Mutation in PLOD gene; lysyl hydroxylase deficiency (enzyme important in collagen cross-linking) Type VI (ocular scoliotic) Arthrochalasis Autosomal dominant Bilateral congenital hip dislocation, severe joint hypermobility, skin hyperextensibility Deletion of type I collagen exons encoding N-terminal end of COL1A1 or COL1A2 Type VIIA, VIIB Dermatosparaxis - Autosomal recessive Severe skin fragility and substantial bruising, sagging or redundant skin Mutation in ADAMTS2 gene; type I procollagen N-terminal peptidase deficiency Type VIIIC Presentation Symptoms double-jointedness easily damaged, bruised, & stretchy skin easy scarring & poor wound healing increased joint mobility, joint popping, early arthritis especially shoulders, patellae, ankles chronic musculoskeletal pain (50%) Physical exam a score of 5 or more on 9-point Beighton-Horan scale defines joint hypermobility ; however this threshold varies in the literature passive hyperextension of each small finger >90° (1 point each) passive abduction of each thumb to the surface of forearm (1 point each) hyperextension of each knee >10° (1 point each) hyperextension of each elbow >10° (1 point each) forward flexion of trunk with palms on floor and knees fully extended (1 point) Imaging Radiographs look for joint dislocations/subluxations kyphoscoliosis Echocardiogram cardiac evaluation with echo is mandatory in the workup up to 1/3 of patients have aortic root dilatation Labs Diagnosed by collagen typing of skin biopsy Treatment Nonoperative physical therapy, orthotics, supportive measures for pain indications login to view 1 more bullet Operative arthrodesis indications login to view 1 more bullet technique login to view 1 more bullet posterior spinal fusion indications login to view 1 more bullet technique login to view 1 more bullet