• Ehlers–Danlos syndrome is a group of connective tissue disorders characterized by joint hypermobility, hyperextensible skin, and fragile connective tissue.
• New classification system describes 6 types:
– Classic type (formerly types I and II, characterized by joint hypermobility, skin laxity and fragility).
– Hypermobility type (formerly type III, characterized by joint hypermobility).
– Vascular type (formerly type IV, complicated by arterial or bowel rupture).
– Kyphoscoliosis type (formerly type VI or ocular-scoliotic type, characterized by globe fragility, scoliosis, and skin and joint laxity).
– Arthrochalasis type (formerly type VIIB, characterized by short stature, joint laxity and dislocations).
– Dermatosparaxis type (formerly type VIIC, characterized by fragile skin with sagging and folding).
– Tenascin-X-deficient type (characterized by joint hypermobility, hyperelastic skin, and fragile tissue).
• The prevalence of Ehlers–Danlos syndrome is reported to be 1 in 5,000–10,000 individuals. However, the disease may be underdiagnosed due to milder presentations.
– The kyphoscoliosis type affects 2% and is 1 of the less common types.
• Varies by type: the kyphoscoliosis and the dermatosparaxis types are autosomal recessive, and the remaining types are autosomal dominant.
• The ADAMTS2, COL1A2, COL3A1, COL5A1, COL5A2, PLOD1, and TNXB genes are all associated with Ehlers–Danlos.
– These genes are responsible for the assembly and modification of collagen molecules.
Gene mutations result in deficient collagen biosynthesis, primarily of types I and III, leading to fragility of collagen-containing structures.
The various types of Ehlers–Danlos syndrome are due to mutations in many genes coding for collagen synthesis or posttranslational modification.
• Family history.
• Muscle weakness.
• Joint pain.
• Easy bruising.
• Dental problems.
• Ocular problems.
• Skin usually white, soft, doughy, hyperextensible, fragile, and with visible underlying vessels.
• Flexible fingers and toes.
• Molluscoid pseudotumors—spongy tumors overlying scars
• Cardiac defects.
– Mitral valve prolapse.
• Abnormal wound healing.
• Increased bleeding (platelet aggregation dysfunction).
• Ocular defects.
– Retinal hemorrhage.
– Retinal detachment (due to stretching of collagenous sclera).
– Lens subluxation.
– Angioid streaks.
– Dry eyes.
– Blue sclera.
– Carotid–cavernous sinus fistula.
– Globe rupture.
– Posterior staphyloma.
• Musculoskeletal features.
– Hyperextensible joints.
– Spontaneous dislocation.
– Kyphoscoliosis (convex curving of the spinal column both backwards and sideways).
– Hallus valgus (bunion).
– Pes planus (flat foot).
– Genu recurvatum (hyperextension of knee).
• Functional bowel disorder.
– Irritable bowel syndrome.
• Nerve compression (carpal tunnel).
DIAGNOSTIC TESTS & INTERPRETATION
• No screening laboratory tests.
• Secondary laboratory testing includes the following:
– Collagen typing.
– Collagen gene mutation testing (see “Genetics”).
– Lysyl oxidase or hydroxylase activity.
• No initial imaging.
• Secondary imaging may show:
– Calcification of nodules opaque on radiographs.
– Joint dislocation/subluxation.
• Echocardiography (mitral valve prolapse).
• Skin biopsy (not sensitive).
• Histology reveals whorled, sparse, and disorderly collagen.
• Irregular diameter of fibrils.
• Loeys–Dietz syndrome.
• Pseudoxanthoma elasticum.
• Turner syndrome.
• Cartilage-hair hypoplasia syndrome.
• Muscular hypotonia.
• Unsatisfactory medical treatments.
• Treatment is largely supportive.
• Vitamin C—cofactor for collagen fibril synthesis.
• Care with surgery (vascular rupture and increased bleeding risk).
• Care with anesthesia (cervical spine and airway trauma).
• Avoidance of contact sports (types IV and VI) due to spontaneous vascular rupture.
• Care with pregnancy—reports of premature rupture of membranes.
Issues for Referral
• Primary care doctor or dermatologist for periodic skin examinations.
• Orthopedics (braces, surgical repair of joints).
• Rehabilitation (physical and occupational therapy).
• Genetic counseling prior to pregnancy.
• The Ehlers–Danlos National Foundation (www.ednf.org).
• Generally patients have a normal lifespan.
• Risk of large vessel or organ rupture with the vascular and kyphoscoliosis types with possible sudden death.
• Organ rupture (uterus or bowel).
• Vessel rupture (aortic aneurysm).
• Globe rupture.
• Beighton P. Serious Ophthalmological complications in the Ehlers-Danlos syndrome. Br J Ophthalmol 54(4):263–268.
• Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos Syndromes: Revised Nosology, Villefranche, 1997. Am J Med Genet 77:31–37.
• Pollack JS, Custer PL, Hart WM, Smith ME, Fitzpatrick MM. Ocular Complications in Ehlers-Danlos Syndrome Type IV. Arch Opthalmol 115:416–419.
• 361.9 Unspecified retinal detachment
• 362.81 Retinal hemorrhage
• 756.83 Ehlers-danlos syndrome
• Ehlers–Danlos is underdiagnosed because of varied presentation.
• The vascular type of Ehlers–Danlos may not present with joint hypermobility or skin hyperelasticity.
• Ehlers–Danlos syndrome is primarily a clinical diagnosis, and most individuals will not likely have any symptoms throughout their lifetime.