You are asked to evaluate a 9-year-old boy with a history of loose baggy scars resulting from wounds on his shins that took 2 months to heal following minor trauma. He is camera shy about his legs but demonstrates his rubbery skin (fig. 1) and double jointedness (fig. 2). What’s the diagnosis?
Diagnosis and Clinical Presentation
Diagnosis: Ehlers-Danlos Syndrome. Ehler’s-Danlos Syndrome (EDS) is a heterogenous group of genetic connective tissue diseases characterized by defects in collagen synthesis, which can affect the skin, ligaments, joints, blood vessels, and internal organs. Clinical hallmarks of disease include joint hypermobility, hyperelasticity of skin, and tissue fragility (1, 2). Classification of EDS began in the late 1960s, with the first international classification system created in 1988 in Berlin, which initially defined nine disease types (designated Type I-IX). However this system did not adequately discriminate between each EDS and EDS with other phenotypically related syndromes. With the elucidation of molecular and genetic basis of disease, a revised classification system (3, 4) was created at a conference in Villefranche, France, which identified 6 specific subtypes of EDS (Table I) defined primarily by the etiology of each syndrome, aided by the clinical features, inheritance pattern, and biochemical and molecular analysis when possible. There is great clinical variability within these syndromes, especially in children, given that the appearance of recognizable symptoms is age-dependent. Previously recognized forms of EDS that are classified as “other” in the new classification system include: X-linked EDS (Type V), the periodontotic type of EDS (Type VIII), fibronectin-deficient EDS (Type X), progeroid form, and unspecified types. These syndromes have only been described in single families, are not well characterized, and may represent EDS-like syndromes. Fragility of the skin is not synonymous with hyperelasticity of the skin. The presence of atrophic scars is thought to be a reflection of tissue fragility, which is why not all patients with hyperelasticity of the skin develop atrophic scars. Atophic scars are most commonly recognized in the classical (types I,II, kyphoscoliosis (type VI), and periodontal types EDS (type VIII). Children with benign hypermobility (type III) EDS do not have tissue fragility. The presence of atrophic scars suggests a diagnosis of the classical type. Due to tissue fragility children can develop lacerations with relatively minor trauma, especially areas prone to injury. Open wounds have a fish mouth appearance with protruding fat lobules. Delayed wound healing is partly attributed to wound dehiscence, which commonly occurs as stitches hold poorly because the thread can cut through skin. After primary wound healing, scars can stretch becoming broad, thin and shiny, giving the appearance of “cigarette paper”, papyraceous, or a “burn scar”. The scars eventually become violaceous and often corrugated by fine wrinkles with repetitive trauma. Easy bruisability is the most common presentation to the pediatrician, often prompting hematologic evaluation for coagulopathy. It is likely a result of fragility of the walls of the small blood vessels and perivascular connective tissue. Children often have bleeding gums with brushing of their teeth.
Epidemiology and pathogenesis
Several mutations or deficiencies of proteins involved in collagen synthesis leading to disturbed collagen fibrillogenesis have been identified (1). However these genetic abnormalities account for a small fraction of EDS cases. The classical type of EDS has been associated with mutations in collagen V. A mutation in the extracellular matrix protein tenascin X has also been identified in some cases.
The differential diagnosis of joint laxity, hyperelastic skin, or tissue fragility is quite broad. Joint hypermobility should be assessed using the Beighton scale. Diseases with joint laxity include Marfan syndrome, certain forms of osteogenesis imperfecta, muscular hypotonia of various causes, and fetal anticonvulsant syndrome. Diseases with hyperelastic skin include Noonan syndrome and cutis laxa syndromes. Bruising can also be a presenting sign in patients with coagulopathies or non-accidental injury. About 90% of patients with EDS have the classical type.
There is no medical treatment for EDS, but preventative measures and physical therapy can help affected individuals cope with symptoms. Non-weight bearing exercise like swimming can improve hypotonia to promote muscle coordination. Activities with high joint strain, high impact, and violent sports should be avoided. Athletic pads and bandages should be used to protect fragile skin, especially in young children.
Our patient’s findings were most suggestive of the diagnosis of the classical type of EDS. We encouraged him to avoid aggressive sports like football and to participate in low impact exercise. We also discussed the use of protective gear to reduce injuries to his legs. WE examined his parents who had no evidence of EDS and referred the family to the Connective Tissue Disease clinic for genetic counseling.
Ehlers-Danlos Syndrome should be considered in any individual with hyperelastic skin with loose baggy scars.
- Steinmann B., Royce PM., and Superti-Furga A. The Ehlers-Danlos Syndrome. In: Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects. 2nd ed. New York, New York: Wiley, 2002.
- Parapia LA and Jackson C. Ehlers-Danlos syndrome – a historical review. Br J Haematol. 2008; 141(1):32-5.
- Grahame R, Bird HA, Child A. The revised (Breighton 1998) Criteria for the diagnosis of Benign Joint Hypermobility Syndrome (BJHMS). J Rheumatol. 2000; 27(7):1777-9.
- Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet. 1998; 77(1):31-7.