Ehlers-Danlos Syndromes Emily Chang AM report May 18, 2009

What is it? A group of inherited disorders with wide phenotypic variability but that involve primarily connective tissues A group of inherited disorders with wide phenotypic variability but that involve primarily connective tissues Often involved are skin, joints, and blood vessel walls Often involved are skin, joints, and blood vessel walls Defects are caused by genetic mutations affecting collagen production Defects are caused by genetic mutations affecting collagen production There are 6 major types (but LOTS of variability) There are 6 major types (but LOTS of variability)

General Symptoms Stretchy skin Stretchy skin Flexible joints with hypermobility Flexible joints with hypermobility Hernias Hernias Abnormal wound healing/stretching scars Abnormal wound healing/stretching scars Joint dislocations Joint dislocations Easy bruising Easy bruising Muscle weakness Muscle weakness Heart and vascular problems such as aneurysms, MVP, aortic root dilatation Heart and vascular problems such as aneurysms, MVP, aortic root dilatation Uterine and intestinal rupture Uterine and intestinal rupture

Joint and Skin Findings

Differential Diagnoses Marfan Syndrome Marfan Syndrome Benign Hypermobility Joint Syndrome Benign Hypermobility Joint Syndrome Diagnosed by Beighton score, Beighton criteria Diagnosed by Beighton score, Beighton criteria Loeys-Dietz Syndrome Loeys-Dietz Syndrome Stickler Syndrome Stickler Syndrome Williams Syndrome Williams Syndrome Aarskog-Scott Syndrome Aarskog-Scott Syndrome Fragile X Syndrome Fragile X Syndrome Achondroplasia, hypochondroplasia Achondroplasia, hypochondroplasia

Classical Type (Types I & II) Generalized hyperextensibility of joints and skin Generalized hyperextensibility of joints and skin Easy bruising, hemarthroses Easy bruising, hemarthroses Poor wound healing and retention of sutures Poor wound healing and retention of sutures Congenital dislocation of hips Congenital dislocation of hips Scoliosis Scoliosis MVP MVP

Hypermobility Type (Type III) Most common type (1 in 10-15,000) Most common type (1 in 10-15,000) Joint hyperextensibility Joint hyperextensibility Chronic degenerative joint disease Chronic degenerative joint disease Less skin involvement Less skin involvement Advanced premature OA with pain Advanced premature OA with pain MVP MVP

Vascular Type (Type IV) Most serious type (1 in 250,000) Most serious type (1 in 250,000) Prone to ruptured/dissected arteries and aneurysms, intestinal and uterine rupture Prone to ruptured/dissected arteries and aneurysms, intestinal and uterine rupture Easy bruising Easy bruising Visible veins beneath thin, translucent skin Visible veins beneath thin, translucent skin Protruding eyes, thin nose/lips, sunken cheeks, small chin Protruding eyes, thin nose/lips, sunken cheeks, small chin Joint involvement variable Joint involvement variable Relative deficiency in type III collagen Relative deficiency in type III collagen

Kyphoscoliosis Type (Type VI) Arthrochalasia Type (Type VIIA/VIIB) Dermatosparaxis Type (Type VIIC)

Genetic Inheritance Primarily Autosomal Dominant Primarily Autosomal Dominant Kyphoscoliosis and dermatosparaxis types are inherited in Autosomal Recessive pattern Kyphoscoliosis and dermatosparaxis types are inherited in Autosomal Recessive pattern

Diagnosis Family History/Pedigree Family History/Pedigree Physical Exam/History Physical Exam/History ECHO ECHO DEXA DEXA Skin biopsy for vascular type Skin biopsy for vascular type Urine test for kyphoscoliosis type Urine test for kyphoscoliosis type Genetic testing for classical, vascular, kyphoscoliosis and arthrochalasis types Genetic testing for classical, vascular, kyphoscoliosis and arthrochalasis types Can do prenatal and pre-implantation testing Can do prenatal and pre-implantation testing

Family Tree ? 13 aortic aneurysm aortic aneurysm, aneurysm of kidney 28 AA 31 AA, cerebral hemorrhage 45 AAA 45 ?valve replacement

Complications Scarring (molluscoid pseudotumors) Scarring (molluscoid pseudotumors) Difficulty healing surgical wounds and sutures that tear out Difficulty healing surgical wounds and sutures that tear out Chronic joint pain and joint dislocations Chronic joint pain and joint dislocations Eye problems – globe rupture Eye problems – globe rupture Premature rupture of membranes Premature rupture of membranes Rupture/dissection of major vessels or organs (uterine, intestinal, aortic) Rupture/dissection of major vessels or organs (uterine, intestinal, aortic)

Treatment Managing sx and preventing complications Managing sx and preventing complications Rehabilitation – PT/OT, aquatic therapy Rehabilitation – PT/OT, aquatic therapy Patient education Patient education Body mechanics Body mechanics NSAIDs, chronic pain management NSAIDs, chronic pain management Orthopedics and possible role for braces Orthopedics and possible role for braces Antibiotic prophylaxis if MVP Antibiotic prophylaxis if MVP Minimize trauma and meticulous hemostasis during surgery Minimize trauma and meticulous hemostasis during surgery Genetic counseling Genetic counseling

References Klippel, John. Primer on the Rheumatic Diseases. Edition 12. Atlanta, GA: Arthritis Foundation; 2001: Klippel, John. Primer on the Rheumatic Diseases. Edition 12. Atlanta, GA: Arthritis Foundation; 2001: Ramanath VS, Oh JK, Sundt III TM, Eagle KA. Acute Aortic Syndromes and Thoracic Aortic Aneurysm. Mayo Clinic Proceedings. 2009; 84(5): Ramanath VS, Oh JK, Sundt III TM, Eagle KA. Acute Aortic Syndromes and Thoracic Aortic Aneurysm. Mayo Clinic Proceedings. 2009; 84(5): Beighton P, DePaepe A, Steinmann B, Tsipouras P and Wenstrup RJ. Ehlers-Danlos Syndromes: Revised Nosology, Villefranche, Am J Med Gen 1998; 77: Beighton P, DePaepe A, Steinmann B, Tsipouras P and Wenstrup RJ. Ehlers-Danlos Syndromes: Revised Nosology, Villefranche, Am J Med Gen 1998; 77:

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