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Osteogenesis imperfectaPROSES PERTUMBUHAN NORMAL

Pertumbuhan tulangPusat osifikasi primerPusat osifikasi sekunderPROSES PERTUMBUHAN NORMAL

Pertumbuhan tulangOsteogenesis imperfecta (OI)disorder of congenital bone fragility caused by mutations in the genes that codify for type I procollagen (ie, COL1A1 and COL1A2).4 types of OI :Type I - Mild formsType II - Extremely severeType III - SevereType IV - Undefined

PathophysiologyType I collagen fibers are found in the bones, organ capsules, fascia, cornea, sclera, tendons, meninges, and dermis. Type I collagen, which constitutes approximately 30% of the human body by weight, is the defective protein in OI.In structural terms, type I collagen fibers are composed of a left-handed helix formed by intertwining of pro-alpha 1 and pro-alpha 2 chains. Mutations in the loci that encode these chains cause OI (ie, COL1A1 on band 17q21 and COL1A2 on band 7q22.1, respectively). Other mutations : bone fragility associated with distinctive clinical or histologic features (eg, redundant callus formation, pseudoglioma, defective mineralization of bone). These conditions have been grouped as syndromes resembling OI.

Cartilage-associated protein (CRTAP) is a protein required for prolyl 3-hydroxylation. Loss of CRTAP in mice causes an osteochondrodysplasia characterized by severe osteoporosis and decreased osteoid production. In humans, CRTAP mutations may be associated with syndromes resembling osteogenesis imperfecta, including recessive forms of lethal syndromes resembling OI and syndromes resembling OI with redundant callus formation.Resembling of OICongenital brittle bones with rhizomeliashort humerus and femora, and recessive inheritance Fractures may be present at birth., the genetic defect has been mapped to the short arm of chromosome 3, where no genes codify type I procollagen.

Congenital brittle bones with redundant callus formationhyperplastic calluses in long bones after having a fracture or orthopedic surgery. Mutations in the type I procollagen genes have not been found Inheritance appears to be autosomal dominant.presentation : OI with bone fragility and deformity, patients develop hard, painful, and warm swellings over long bones Patients with this condition have white sclera and normal teeth.On radiographs, a redundant callus can be observed around some fractures. Osteoporosis pseudoglioma syndromean autosomal recessive . Bone fragility is mild to moderate. Blindness is due to hyperplasia of the vitreous, to corneal opacity, and to secondary glaucoma. The genetic defect has been identified and mapped to chromosomal region 11q12-13. The defect is specifically in the LRP5 gene that encodes for the low-density lipoprotein receptor-related protein 5.

Other ocular formsAt least 2 other forms with ocular involvement are described in the literature. One variant includes optic atrophy, retinopathy, and severe psychomotor retardation; another variant includes microcephaly and cataracts.etcEpidemiologyThe prevalence of OI : 1 per 20,000 live births; however, the mild form is underdiagnosed, and the actual prevalence may be higher.Prevalences appear to be similar worldwide, increased rate in Zimbabwe.No differences based on race and sexTh e age begin widely varies. mild forms may not have fractures until adulthood, or they may present with fractures in infancy. severe cases present with fractures in utero.Patients often have a family history of osteogenesis imperfecta (OI), but most cases are due to new mutations.Patients most commonly present with fractures after minor trauma.In severe cases, prenatal screening ultrasonography performed during the second trimester may show bowing of long bones, fractures, limb shortening, and decreased skull echogenicity. Lethal OI cannot be diagnosed with certainty in utero.Patients may bruise easily.Patients may have repeated fractures after mild trauma. However, these fractures heal readily.Deafness is another feature. About 50% of patients with type I OI have deafness by the age 40.Type I - Mild formsPatients have no long-bone deformity.The sclera can be blue or white. Dentinogenesis imperfecta may be present.Over a lifetime, numbers of fractures can range from 1-60.Height is usually normal in individuals with mild forms of OI.People with OI have a high tolerance for pain. Exercise tolerance and muscle strength are significantly reduced in patients with OIFractures are most common during infancy Other possible findings : kyphoscoliosis, hearing loss, premature arcus senilis, and easy bruising.

Type II - Extremely severeType II is often lethal.Blue sclera may be present.Patients may have a small nose, micrognathia, or both.All patients have in utero fractures, which may involved the skull, long bones, and/or vertebrae.The ribs are beaded, and the long bones are severely deformed.Causes of death include extreme fragility of the ribs, pulmonary hypoplasia, and malformations or hemorrhages of the CNS.

Type III - Severejoint hyperlaxity, muscle weakness, chronic unremitting bone pain, and skull deformities (eg, posterior flattening) due to bone fragility during infancy.Deformities of upper limbs may compromise function and mobility.dentinogenesis imperfecta The sclera have variable hues.In utero fractures are common.Limb shortening and progressive deformitiestriangular face with frontal bossing.Basilar invagination uncommon, but potentially fatal occurrence in OI.Vertigo is commonHypercalciuria : 36% of patientsRespiratory complications secondary to kyphoscoliosis Constipation and hernias

Type IV - UndefinedThis type of OI is not clearly defined.Whether patient have normal height or whether scleral hue defines the type has not been established in consensus.Dentinogenesis imperfecta may be present. Fractures usually begin in infancy, but in utero fractures may occur. The long bones are usually bowed.Other Problems to Be ConsideredCamptomelic dysplasiaAchondrogenesis type ICongenital hypophosphatasiaSteroid induced osteoporosisBattered child syndrome (syndrome X)Idiopathic juvenile osteoporosisLaboratory Studiesroutine laboratory studies are normalCollagen synthesis is performed by culturing dermal fibroblasts. Results are negative in syndromes resembling OIPrenatal DNA mutation analysis can be performed in pregnancies (chorionic villus cells). Bone mineral density, as measured with dual-energy x-ray absorptiometry (DEXA), is low in children and adults with OI despite the severity. Histologic Findingsthe width of the cortex, and the volume of cancellous bone are decreasedthickness of trabeculae are reduced.defects in modeling of external bone in terms of the size and shape, OI might be regarded as a disease of the osteoblast.Bone formation is quantitatively decreased, Medical CareOI is a genetic condition, it has no cure.Cyclic administration of intravenous pamidronate reduces the incidence of fracture and increases bone mineral density, Nutritional evaluation and intervention are paramount to ensure appropriate intake of calcium and vitamin D. Caloric management is important, particularly in adolescents and adults with severe forms of OI.

.Surgical CareOrthopedic surgery is one of the pillars of treatment for patients with OI. Surgical interventions include intramedullary rod placement, surgery to manage basilar impression, and correction of scoliosisConsultationsCare of OI patients is multidisciplinary. Team members may include an occupational therapist (OT), a physical therapist (PT), nutritionist, an audiologist, an orthopedic surgeon, neurosurgeon, pneumologist, and nephrologist, among others.Offer genetic counseling to the parents of a child with OI

DietAdequate calcium, vitamin D, and phosphorus intake are paramount.Caloric management is necessary in nonambulatory patients with severe OI.

ActivityParents need special instructions in handling affected children.Parents need to know how to position the child in the crib and how hold the child to avoid causing fractures while maintaining bonding and physical stimulation.

ComplicationsRecurrent PneumoniaHeart FailureBrain DamagePermanent deformityBreathing ProblemsHearing lost

KONDROBLASTZONAPROLIFERASIZONAHIPERTROFIZONA KALSIFIKASIZONAOSIFIKASIOSSIFIKASI ENDOKONDRAL PADAZONA TULANG RAWAN EPIFISISOsteoblastmenyusupAKONDROPLASIAXMENINGKATKAN KOLAGEN & MATRIXFGFNORMAL:KECEPATAN PROLIFERASI& DESTRUKSI, SEIMBANGGAMBARAN KLINIKPerawakan pendekRhizomeliaMidfacial hypoplasia, frontal bossingProminent foerhead

Gibbus torakolumbalMegalencepahly, contracted skull basePenyempitan ruang interpedikelBrachidactily, trident handANTROPOMETRI

BB : 4,8 KGPB : 60 CMLK : 44 CM

Tinggi duduk : 42 cmArm span : 52 cmPanjang lengan 13 cm( segmen atas ( 6 cm )Panjang tungkai 22 cm( segmen atas 12 cm )Arm spanUpper( U )Lower( L )

ACHONDROPLASIAMarfan syndromeMarfan syndrome is an inherited connective tissue transmitted as an autosomal dominant trait. Inherited connectice tissue disordersBonesLigamentsEyesLungBlood vesselsHeart (weakness of the aorta)

MARFAN SYNDROME

Pathophysiologymutations in the fibrillin-1 (FBN1) gene ( chromosome 15q21.1) The gene encodes the glycoprotein fibrillin, a major building block of microfibrils, which constitute the structural components of the suspensory ligament of the lens and serve as substrates for elastin in the aorta and other connective tissues. Fibrillin-1 ( a large glycoprotein ) is a main component of the 10-12 nm extracellular microfibrils that are important for elastogenesis, elasticity, and homeostasis of elastic fibres. ManifestationsTall, arachnodactyly , long fingers and hypermobile joints, is seen in the majority of patient. Feet are flatSpine may be curved, Low back pain near the tailbone Face; long & narrow, high palateCrowded teethDislocation of the eye lensEnlarged of the aorta near the heartLeakage of the aortic valve, a decrescendo diastolic murmur, dysrhythmia Dyspnea, severe palpitations, and substernal pain in severe pectus excavatumBreathlessness, often with chest pain, in spontaneous pneumothoraxDiagnosis of Marfan syndrome currently is made using a set of diagnostic criteria that is based on evaluation of family history, molecular data, and 6 organ systems. Berlin criteria, the diagnosis of Marfan syndrome diagnosed was based on involvement of the skeletal system and 2 other systems, with the requirement of at least 1 major manifestation (ectopia lentis, aortic dilatation or dissection, or dural ectasia).3,9 Skeletal systemMarfan syndrome diagnosed was based on involvement of the skeletal system and 2 other systems, with the requirement of at least 1 major manifestation (ectopia lentis, aortic dilatation or dissection, or dural ectasia).Ocularmajor criteria: ectopia lentis. About 50% of patients have lens dislocation. Minor criteria : Flat cornea (measured by keratometry) , The most common refraction error is myopia due to elongated globe and amblyopia. Glaucoma (patients