CONNECTIVE TISSUECONNECTIVE TISSUE INTRODUCTION & HERITABLE DISORDERS

Suresh.M

DEFINITIONDEFINITION

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 CollagenStructure of Collagen

Collagen has a triple helix structureThree 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.

CLASSIFICATIONCLASSIFICATION

Heritable Disorders- Marfans syndrome Osteogenesis

imperfecta Ehler-Danlos syndrome Epidermolysis bullosa Alport syndromeAutoimmune Disorders- SLE,

Rheumatoid arthritis, scleroderma, Sjogrens syndrome and Vasculitis.

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

PathogenesisPathogenesisMFS1- 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 featuresClinical features

Long limbsLong limbs

ArachnodactylyArachnodactyly

High arched palateHigh arched palate

Cvs manifestationsCvs manifestations aortic

aneurysm aortic root

dilatation mitral prolapse mitral

regurgitation

Ocular featuresOcular features

CNS manifestationsCNS manifestations

Dural ectasia- weakening of connective tissue

of Dural sacManifests as low back pain, leg

pain which relieves on lying down

Other features- spontaneous

pneumothorax inguinal hernia incisional hernias

DiagnosisDiagnosisGhent's criterion-four skeletal abnormalities & one

or more signs in other systems like cvs or ocular.

A positive family history is very helpful.

TreatmentTreatment

Beta blockersValvuloplastyStentsMechanical bracingIol placement

Osteogenesis imperfectaOsteogenesis imperfecta

Characterized by generalized osteopenia, brittle bones due to defective synthesis of collagen type1.

Autosomal dominant disorder.Incidence is 1 in 30000.

pathogenesispathogenesis

Mutations in COL1A1,COL1A2

Abnormal proalpha chain

Failure of triple helix formation

Procollagen suicide

Thin collagen fibers are formed

Clinical featuresClinical features

Bone deformityBone deformity

Fractures inuteroFractures inutero

Multiple rib fracturesMultiple rib fractures

Dislocation of radial headDislocation of radial head

Blue scleraBlue sclera

Other featuresOther features

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

TreatmentTreatment

PhysiotherapySurgical management of fractures

& skeletal deformities.Stapedectomy and prosthesis

replacement.Biphosphonates to reduce bone

loss.

Ehlers-Dantos syndromeEhlers-Dantos syndrome

Characterized by hyper elasticity of skin and hyper mobility of joints.

Mostly Autosomal dominant.Incidence is 1 in 5000.Defect in collagen type5 and

collagen type3.

Clinical featuresClinical features

Hyper mobility of jointsHyper mobility of joints

Rubber man syndromeRubber man syndrome

Other featuresOther features

Cigarette paper scar.Easy bruisability.Dislocations of hipMitral valve prolapse.Hernias.

TreatmentTreatment

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 diseasesElastin related diseasesEpidermolysis bullosa- Characterized by blister formation

following minor trauma.Types- EB simplex EB hemidesmosal EB junctional EB dystrophicaTreatment is symptomatic

Alport syndromeAlport syndrome

Characterized by hematuria, sensorineural deafness, lenticonus.

X-linked disorder.Incidence is 1 in 10000.Hematuria gradually leads to

nephritis which ultimately cause renal failure.

Treatment- Renal transplantation

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