CONNECTIVE TISSUE CONNECTIVE TISSUE INTRODUCTION & HERITABLE DISORDERS Suresh.M

DEFINITION Connective tissue is a type of fibrous tissue composed of insoluble matrix in which complex molecules (collagen) are assembled. Major constituents- Collagen, Elastin Collagen is defective in most of the connective tissue disorders

Structure of Collagen Collagen has a triple helix structure Three polypeptide chains(alpha1,2,3) Each chain has 1000 amino acids. Every third amino acid must be Glycine. There are 28 types of collagens which differ in amino acid sequence.

CLASSIFICATION Heritable Disorders- Marfans syndrome Osteogenesis imperfecta Ehler-Danlos syndrome Epidermolysis bullosa Alport syndrome Autoimmune Disorders- SLE, Rheumatoid arthritis, scleroderma, Sjogrens syndrome and Vasculitis.

Marfans Syndrome Triad of features- Skeletal abnormalities Reduced Vision Aortic aneurysm Inherited as autosomal dominant disorder. Types- MFS1(90%) MFS2 Loeys-Dietz aneurysm syndrome Congenital contractual arachnodactyly

Pathogenesis MFS1- mutation of FBN1 Defective synthesis of Fibrillin1 Decreased mech integrity of Elastin Laxity of suspensory ligaments Dilatation of aorta, skeletal defects

MFS2- Mutation in TGFB2 Loeys-Dietz aneurysm syndrome- Mutation in TGFB1,TGFB2 Congenital contractual arachnodactyly- Defect in Fibrillin1,fibrillin2

Clinical features Clinical features

Long limbs

Arachnodactyly

High arched palate High arched palate

Cvs manifestations aortic aneurysm aortic root dilatation mitral prolapse mitral regurgitation

Ocular features Ocular features

CNS manifestations Dural ectasia- weakening of connective tissue of Dural sac Manifests as low back pain, leg pain which relieves on lying down

Other features- spontaneous pneumothorax inguinal hernia incisional hernias

Diagnosis Ghent's criterion- four skeletal abnormalities & one or more signs in other systems like cvs or ocular. A positive family history is very helpful.

Treatment Beta blockers Valvuloplasty Stents Mechanical bracing Iol placement

Osteogenesis imperfecta Characterized by generalized osteopenia, brittle bones due to defective synthesis of collagen type1. Autosomal dominant disorder. Incidence is 1 in

pathogenesis pathogenesis Mutations in COL1A1,COL1A2 Abnormal proalpha chain Failure of triple helix formation Procollagen suicide Thin collagen fibers are formed

Clinical features Clinical features

Bone deformity Bone deformity

Fractures inutero Fractures inutero

Multiple rib fractures Multiple rib fractures

Dislocation of radial head Dislocation of radial head

Blue sclera Blue sclera

Other features Kyphoscoliosis. Amber/bluish colored teeth. Progressive hearing loss. Aortic & mitral regurgitation. Fragility of large blood vessels.

Treatment Physiotherapy Surgical management of fractures & skeletal deformities. Stapedectomy and prosthesis replacement. Biphosphonates to reduce bone loss.

Ehlers-Dantos syndrome Characterized by hyper elasticity of skin and hyper mobility of joints. Mostly Autosomal dominant. Incidence is 1 in Defect in collagen type5 and collagen type3.

Clinical features Clinical features

Hyper mobility of joints Hyper mobility of joints

Rubber man syndrome Rubber man syndrome

Other features Cigarette paper scar. Easy bruisability. Dislocations of hip Mitral valve prolapse. Hernias.

Treatment Surgical repair & tightening of joint ligaments. Easy bruisability should be differentiated from bleeding disorders. Counseling to women about uterine rupture and bleeding during pregnancy.

Elastin related diseases Epidermolysis bullosa- Characterized by blister formation following minor trauma. Types- EB simplex EB hemidesmosal EB junctional EB dystrophica  Treatment is symptomatic

Alport syndrome Alport syndrome Characterized by hematuria, sensorineural deafness, lenticonus. X-linked disorder. Incidence is 1 in Hematuria gradually leads to nephritis which ultimately cause renal failure. Treatment- Renal transplantation

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