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ALBERT C.YANMDSAMIR S.SHAHMD
Denouement and Discussion: Ehlers-Danlos Syndrome, Classical Type
Ehlers-Danlos syndrome is a heterogenous group of inherited connective tissue disorders characterized by the variable expression of hyperextensible skin, joint hypermobility, and tissue fragility.1 Ehlers-Danlos syndrome is thought to occur as frequently as 1 in 5000 and can affect any sex or race.2 In 1997, a revised classification of Ehlers-Danlos syndrome resulted in a simplified classification of 6 types.3 The new classification system proposed specific major and minor diagnostic criteria for each type and also included newly available molecular and biochemical data.3 The 6 types include classical, hypermobility, vascular, kyphoscoliosis, arthrochalasia, dermatosparaxis, and other.3 The inheritance pattern is either autosomal dominant or autosomal recessive depending on the specific subtype. Severity of symptoms can range from extremely mild to disabling. Because of the varied clinical symptoms, diagnosis can be difficult to make.
The classical type of Ehlers-Danlos syndrome is the most common.1 It is usually transmitted in an autosomal dominant pattern. The major clinical criteria for the classical type include skin hyperextensibility, widened atrophic scars (manifestation of tissue fragility), and joint hypermobility as assessed by the Beighton scale.3 The presence of 1 or more major criteria is necessary to make a clinical diagnosis. Minor criteria are less specific but include smooth, velvety skin; molluscoid pseudotumors; subcutaneous spheroids; recurrent sprains, subluxations, or dislocations; muscle hypotonia; easy bruising; and history of surgical complications.3 The skin manifestations can range in severity from barely perceivable to severe. Easy bruising and pronounced scar formation in areas of trauma are often the initial symptoms in early childhood. Because of increased bruising, affected children are frequently evaluated for a bleeding disorder before a diagnosis of Ehlers-Danlos syndrome is made.4 The classical type usually does not have associated life-threatening systemic abnormalities; however, workup to rule out more severe types of Ehlers-Danlos syndrome is often warranted. The differential diagnosis for Ehlers-Danlos syndrome includes nonaccidental trauma (due to easy bruising and scarring), bleeding disorders, and cutis laxa.4
Associated systemic features
Individuals with all types of Ehlers-Danlos syndrome are at risk for mitral valve prolapse and rarely, for aortic dilatation. In addition, individuals with the hypermobility type may have increased joint dislocations and chronic joint/limb pain. Individuals with the vascular type may be at risk for developing a life-threatening, medium-sized arterial rupture. Those with the kyphoscoliosis type may have associated hypotonia, scoliosis, and scleral fragility as well as an increased risk of ocular globe rupture.1 Since some of these abnormalities may result in significant morbidity, appropriate diagnosis and anticipatory guidance are imperative.
Ehlers-Danlos syndrome is a connective tissue disorder resulting from abnormal collagen synthesis. Type I, III, or V collagen can be affected, depending on the exact type of Ehlers-Danlos syndrome.1 The classical type is due to an abnormality in the synthesis of collagen type V and has been linked to a mutation in the COL5A1 or COL5A2 gene.5 Although identification of a gene mutation may confirm a diagnosis, absence of a mutation does not definitively rule out a diagnosis of classical Ehlers-Danlos syndrome, especially if suggestive clinical features are present.3
There is no effective treatment for Ehlers-Danlos syndrome. Palliative and preventive care are the mainstay of management.6 Early diagnosis will allow the health care professional to monitor for possible future complications. Genetic counseling may be helpful for families of affected individuals.4 Physical therapy and orthopedic care may be required for those with significant joint disease. Affected individuals are recommended to avoid high impact or contact sports and may need to modify their activities to limit stress on their joints.6 The Ehlers-Danlos National Foundation can be a helpful source of information (www.ednf.org).
Correspondence: Kimberly A. Horii, MD, Section of Dermatology, Children's Mercy Hospital, 2401 Gillham Rd, Kansas City, MO 64108 (email@example.com).
Accepted for Publication: October 31, 2005.
Author Contributions:Study concept and design: Horii, Nopper, and Sharma. Drafting of the manuscript: Horii and Sharma. Critical revision of the manuscript for important intellectual content: Nopper. Administrative, technical, and material support: Horii and Sharma. Study supervision: Nopper.
Picture of the Month—Diagnosis. Arch Pediatr Adolesc Med. 2006;160(7):706. doi:10.1001/archpedi.160.7.705-b
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