Ehlers-Danlos Syndrome - Pediatrics

Introduction
Connective tissue disorder characterized by hyperelastic/fragile skin joint hypermobility and dislocation generalized ligamentous laxity poor wound healing early onset arthritis additional features soft tissue and bone fragility soft tissue calcification mitral valve prolapse aortic root dilatation developmental dysplasia of the hip clubfoot pes planus scoliosis high palate gastroparesis Genetics COL5A1 or COL5A2 mutation in 40-50% gene for type V collagen important in proper assembly of skin matrix collagen fibrils and basement membrane less common mutations identified below
Classification
Berlin Classification (1988) - revised Types I - XI exist Types II and III - most common and least disabling Villefranche Classification (1998) Classical - Type I (gravis) and Type II (mitis) autosomal dominant hyperextensible skin, widened atrophic scars, joint hypermobility COL5A1 or COL5A2 mutation; type V collagen (co-expressed with type I collagen) Hypermobility - Type III (hypermobile) autosomal dominant large and small joint hypermobility, recurring joint subluxations/dislocations, velvety soft skin, chronic pain, scoliosis unknown mutation Vascular - Type IV (vascular) autosomal dominant, rarely autosomal recessive translucent skin, arterial/intestinal/uterine fragility and spontaneous rupture, extensive bruising COL3A1 mutation; abnormal type III collagen Kyphoscoliosis - Type VI (ocular scoliotic) 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) Arthrochalasis - Type VIIA, VIIB 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 Dermatosparaxis - Type VIIIC autosomal recessive severe skin fragility and substantial bruising, sagging or redundant skin mutation in ADAMTS2 gene; type I procollagen N-terminal peptidase deficiency
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 mainstay of treatment Operative arthrodesis indications joints recalcitrant to non-operative management technique soft tissue procedures are unlikely successful in hypermobile joints posterior spinal fusion indications progressive scoliosis (most common in Kyphoscoliosis Type) technique longer fusions needed to prevent junctional problems