Syndrome

BASICS


DESCRIPTION


• 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).


EPIDEMIOLOGY


Prevalence


• 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.


RISK FACTORS


Genetics


• 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.


GENERAL PREVENTION


Genetic counseling.


PATHOPHYSIOLOGY


Gene mutations result in deficient collagen biosynthesis, primarily of types I and III, leading to fragility of collagen-containing structures.


ETIOLOGY


The various types of Ehlers–Danlos syndrome are due to mutations in many genes coding for collagen synthesis or posttranslational modification.


DIAGNOSIS


HISTORY


• Family history.


• Muscle weakness.


• Joint pain.


• Easy bruising.


• Dental problems.


• Ocular problems.


PHYSICAL EXAM


• 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.


– Dysautonomia.


• Abnormal wound healing.


• Increased bleeding (platelet aggregation dysfunction).


• Ocular defects.


– Retinal hemorrhage.


– Retinal detachment (due to stretching of collagenous sclera).


– Keratoconus.


– Lens subluxation.


– Angioid streaks.


– Dry eyes.


– Strabismus.


– Glaucoma.


– Blue sclera.


– Carotid–cavernous sinus fistula.


– Globe rupture.


– Myopia.


– Posterior staphyloma.


– Photophobia.


• Musculoskeletal features.


– Hyperextensible joints.


– Spontaneous dislocation.


– Sprain.


– Subluxation.


– 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.


– Gastritis.


– Irritable bowel syndrome.


• Nerve compression (carpal tunnel).


DIAGNOSTIC TESTS & INTERPRETATION


Lab


• No screening laboratory tests.


• Secondary laboratory testing includes the following:


– Collagen typing.


– Collagen gene mutation testing (see “Genetics”).


– Lysyl oxidase or hydroxylase activity.


Imaging


• No initial imaging.


• Secondary imaging may show:


– Calcification of nodules opaque on radiographs.


– Joint dislocation/subluxation.


Diagnostic Procedures/Other


• Echocardiography (mitral valve prolapse).


• Skin biopsy (not sensitive).


Pathological Findings


• Histology reveals whorled, sparse, and disorderly collagen.


• Irregular diameter of fibrils.


DIFFERENTIAL DIAGNOSIS


• Elastolysis.


• Loeys–Dietz syndrome.


• Pseudoxanthoma elasticum.


• Turner syndrome.


• Cartilage-hair hypoplasia syndrome.


• Muscular hypotonia.


TREATMENT


MEDICATION


First Line


• Unsatisfactory medical treatments.


• Treatment is largely supportive.


Second Line


• Vitamin C—cofactor for collagen fibril synthesis.


ADDITIONAL TREATMENT


General Measures


• 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


• Ophthalmology.


• Dental.


• Orthopedics.


ONGOING CARE


FOLLOW-UP RECOMMENDATIONS


• Ophthalmology.


• 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.


PATIENT EDUCATION


• The Ehlers–Danlos National Foundation (www.ednf.org).


PROGNOSIS


• Generally patients have a normal lifespan.


• Risk of large vessel or organ rupture with the vascular and kyphoscoliosis types with possible sudden death.


COMPLICATIONS


• Organ rupture (uterus or bowel).


• Vessel rupture (aortic aneurysm).


• Globe rupture.


• Arthritis.


ADDITIONAL READING


• 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.


CODES


ICD9


361.9 Unspecified retinal detachment


362.81 Retinal hemorrhage


756.83 Ehlers-danlos syndrome


CLINICAL PEARLS


• 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.


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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Syndrome
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