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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