Hyperguides

Orthopaedics / Paediatric orthopaedics

Ehlers-Danlos Syndrome

Michelle Cameron, MD Paul D. Sponseller, MD
Article

Introduction

Ehlers-Danlos syndrome (EDS) is a family of disorders caused by a variety of defects in collagen metabolism (Slide 1). The cardinal feature, common through all subtypes of this syndrome, is hyperelasticity of the skin. In addition to hyperextensibility of skin, joint hypermobility, easy bruisability, soft tissue and bony fragility, calcification of soft tissues, and varying degrees of osteopenia are also present.1 Diagnosis is primarily clinical and at least 10 types of EDS have been described.2,3 The more common forms are summarized in Table 1.

Table 1 Slide 1

Abbreviations: AD=autosomal dominant and AR=autosomal recessive.

Another classification system has been proposed recently by Beighton et al.2 This classification simplifies the condition into 6 categories:

  • Classic type. This includes EDS types I and II. It is characterized by hyperextensibility of the skin, tissue fragility, and joint hypermobility. Biochemical studies have revealed defects in type V collagen although locus heterogeneity is present.
  • Hypermobility type. This is EDS type III and is characterized by hyperextensibility of the skin and joint hypermobility, as well as chronic pain in the joints and extremities.
  • Vascular type. EDS type IV is characterized by thin, translucent skin, arterial fragility and rupture, clubfoot, and varicose veins. This type is caused by a mutation in the gene for type III collagen.
  • Kyphoscoliosis type. EDS type IV characterized by muscular hypotonia, scoliosis at birth, rupture of the ocular globe, and osteopenia. It is due to a deficiency of lysyl hydroxylase. It is diagnosed by measurement of urine pyridinoline and deoxypyridinoline crosslinks.
  • Arthrochalasia type. EDS type VII is caused by defects in the gene for type I collagen. Mutations in the alpha-1 chain cause different manifestations than those in the alpha-2 chain. The mechanism by which this causes defects in the final structure of collagen is shown in Slide 1. Clinical manifestations include developmental dislocation of the hip at birth, subluxation of other joints, hypermobility, scoliosis, easy bruisability, and milt osteopenia.
  • Dermatosparaxis type. EDS type VIII is characterized by sagging, redundant skin. It is caused by a deficiency of the enzyme type I procollagen N-terminal peptidase and is autosomal recessive.
Slide 1

On the basis of the previous discussion, it should be noted that the classification is changing as molecular genetic understanding progresses. The orthopedic surgeon must be able to diagnose the syndrome and understand the range of clinical signs and symptoms, as well as understand the kind of genetic defects causing the syndrome.

Clinical Features

EDS types I and II are characterized by generalized hyperextensibility of joints. Other features include bruising, fragility of the skin, and poor retention of surgical sutures.1 Orthopedic symptoms are the consequences of loose-jointedness and include hip dislocation in the newborn, multiple other joint dislocations in later life, joint effusions, clubfeet, spondylolisthesis, and scoliosis.

EDS type III is predominantly characterized by joint hypermobility. Hypermobility can result in dislocations of commonly dislocated joints, such as the shoulder. Overall, many of these patients have minimal disability.

EDS type IV is the most serious type of EDS because of the propensity for spontaneous rupture of the bowel and arteries. Joint hypermobility is limited in this form, and a majority of patients do not present with significant orthopedic problems.

Except for its inheritance pattern, EDS type V closely resembles EDS type II.

The hallmarks of EDS type VI include a fragile ocular globe and severe scoliosis, in addition to joint laxity and dislocations.

Loose joints with congenital dislocations is the dominant clinical feature in EDS type VII.1,2,4 Children are born with dislocations of the hips (Slide 2) and knee subluxation may develop. Other signs that may be diagnostic include dysplasia of the proximal ulna (Slide 3), shortened distal phalanges (Slide 4), and multiple wormian or inclusion bones in the cranial sutures (Slide 5).

Slide 2 Slide 3

Slide 4 Slide 5

EDS type VIII is rare and is characterized by severe periodontal disease with early loss of primary and adult teeth. EDS type IX is primarily characterized by skin laxity. EDS type X is similar to EDS type II with the addition of abnormal platelet aggregation.

Many patients with EDS are diagnosed only after the onset of musculoskeletal symptoms. Because the diagnosis is primarily clinical, referral to a geneticist is appropriate upon suspicion of the condition. Many patients have chronic joint aches and pains that cannot always be explained by clinical or radiographic findings.

Treatment

Due to the heterogeneity of this disease, treatment must be individualized. General treatment principles include counseling the patient regarding appropriate sports, dissuading children from demonstrating joint laxity to friends, reducing congenitally dislocated joints, and strengthening of periarticular muscles in an attempt to increase joint stability.

Operative treatment is often necessary for joint instability and scoliosis. Knowing the subtype of EDS the patient has is often helpful in anticipating perioperative risks and complications. For example, the results after treatment of congenital dislocation of the hip in EDS are not as successful as in idiopathic dislocation. Reconstructive surgery for knee or shoulder subluxation must be undertaken only for patients who have disabling symptoms after an extended period of conservative treatment. In general, the results of soft tissue stabilization for joint subluxation (i.e., shoulder and knee instability) are less predictable than individuals without EDS. A preoperative genetics consultation may be helpful.

References
  1. Giunta C, Superti-Furga A, Spranger S, et al. Ehlers-Danlos syndrome type VII: Clincal features and molecular defects. J Bone Joint Surg. 1999; 81A:225-239.


  2. Beighton P, dePaepe A, Steinmann B, et al. Ehlers-Danlos syndromes: Revised nosology. Am J Med Genet. 1998; 77:31-37.


  3. Dietz FR, Matthews K. Genetic basis of inherited diseases of orthopaedic importance. J Bone Joint Surg. 1996; 78A:1583-1598.


  4. Zaleske DJ. Genetic diseases. In: Morrissy RT, Weinstein SL, eds. Lovell and Winter’s Pediatric Orthopaedics. 4th ed. Philadelphia, Pa: Lippincott-Raven; 1996:181-182.