Osteogenesis imperfecta

PRESENTED BY

Dr. Mahesh ChaudharyMD (RESIDENT) PHASE-B

RADIOLOGY & IMAGING DEPARTMENTBSMMU, DHAKA

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Osteogenesis imperfecta

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It is genetically heterogeneous group of collagen disorders. It is also known as brittle bones disease/ fragilitas ossium.It results from a defect of type I collagen production (major protein of bone matrix) that leads to congenital osteopenia with increased bone fragility, low bone mass, and other connective tissue manifestations like dental abnormalities, lax joints, thin skin.It is a heritable condition of connective tissue.

Osteogenesis imperfecta

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It occurs in 1:20,000 to 1:60,000 of live births. It occurs with equal frequency among males and females and across races and ethnic groups.The hallmark feature of OI is fragile bones that fracture easily.Classical clinical triad of OI is fragility of bone, blue sclera, and deafness (due to ankylosis of ossicles & osteosclerosis) .OI affects both bone quality and bone mass.In some people, height, hearing, skin, blood vessels, muscles, tendons, and teeth may also be affected.

Osteogenesis imperfecta

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It is probably the most common form of skeletal dysplasia requiring substantial orthopaedic care. Although the disease is usually apparent at birth or in childhood, more mild forms of the disease may not become apparent until adulthood, when affected individuals may present with insufficiency fractures and osteopenia.In the more severely affected fetuses antenatal diagnosis may often be made in the second trimester on the basis of shortened long bones with multiple fractures. The thorax tends to be short but not narrow.

Osteogenesis imperfecta

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PathophysiologyIn most cases, OI is caused by a dominant mutation in the COL1A1 or the COL1A2 genes that encode type I collagen. Fewer than 10 percent of OI cases are believed to be caused by recessive mutations in other genes in the collagen pathway.Here is the production of abnormal collagen I molecules as well as a decrease in the production of normal collagen I molecules. This results from mutations in the loci coding for pro-α 1 and pro-α 2 chains which form the helical structure of collagen 1.

Radiographic features

Radiographic features vary according to the type of disease and its severity and include osteopenia and fractures, which may heal with florid callus formation, mimicking osteosarcoma. Bones are thin and under-tubulated (gracile), normal in length or shortened, thickened and deformed by multiple fractures. Intra-sutural (Wormian) bones can be identified on skull radiographs.

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Radiographic features

In severe forms of osteogenesis imperfecta the diagnosis may be made before birth by detailed ultrasound in the second trimester. Diagnostic features include cranial enlargement, reduced echogenicity of bone and deformity and shortening of limb bones as a result of intrauterine fractures.

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Classification of Osteogenesis imperfecta

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The classification of osteogenesis imperfecta is that devised by Sillence et al in 1979 and modified in 1986. The important characteristics in this classification include blue scleraseverity of the disorder & the mode of inheritance (dominant, recessive,

sporadic/new mutation) However accurate classification is difficult

because of phenotypic overlap.

Osteogenesis Imperfecta

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Two forms:Congenita-Life expectancy short. Tarda-Life expectancy is normal

Types: 4 typesOsteogenesis Imperfecta Type IOsteogenesis Imperfecta Type IIOsteogenesis Imperfecta Type IIIOsteogenesis Imperfecta Type IV

Osteogenesis Imperfecta-Type I

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A mild form of this condition (occurs in 70% cases).It has autosomal dominance inheritance.Sclera becomes blue.Bone fragility mild. Fracture rates in childhood diminish with increasing skeletal maturity only to increase again in middle life, particularly in postmenopausal womenStature is normal or only mildly reduced.Deafness occurs in adult life.People suffering from it can expect to live as long as any normal individual.

Osteogenesis Imperfecta- Type I

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Subdivision: Group A: No dental involvement but presence

of minor skeletal changes. Group B: Subjects with dentinogenesis

imperfecta & more severe skeletal changes.Osteoporosis occurs with cortical thinning with bowed thin gracile long bones.In 10% fractures are seen at birth. Most fracture occurs in young children. Wormian bones are seen in skull.

Osteogenesis Imperfecta Type II

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It is generally estimated to be the most severe type of OI.Individuals with Osteogenesis Imperfecta Type 2 generally die within the first year of their life.Sclera are blue.Overall bones are grossly demineralised with thin cortices. Numerous healing or healed fractures are seen at birth despite protection of amniotic fluid. Fractures are occurs during delivery.

Osteogenesis Imperfecta Type II

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Sub types: Type 2A: The long bones are bowed, short and broad. Numerous fractures are seen. The ribs are broad with continuous beading.Type 2B: The long bones are as in Type 2A, but the ribs show no beading or less beading.Type 2C: The long bones are thinned, shows numerous fractures and the ribs too are thin & beaded.

Osteogenesis imperfecta.

Osteogenesis imperfecta.

The child is stillborn. Multiple fractures are demonstrated in the short and broad long bones, which are cystic in appearance. Numerous rib fractures are seen.

Osteogenesis imperfecta congenita (type II)

OI type II in a fetus.

There are fractures in all the long bones.

Multiple fractures are present in the ribs, leading to shortened ribs with a characteristically “ beaded ” appearance.

Also there is poor ossification of the skull

Osteogenesis Imperfecta- Type III

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This occurs in 15% of the patients, is a severe and progressively deforming type & is usually due to new mutation. Affected individuals suffer from multiple fractures that start from the initial years of their life result in bowing. Overall bones are demineralised. Vertebral compression is seen and a kyphoscoliosis results. The long bones are osteoporotic and thin.Sclera may be blue at birth but are usually normal in adolescence. In skull ossification is poor, sutures are wide and wormian bones persists. It also has association with dentinogenesis imperfecta.

Osteogenesis Imperfecta- Type IV

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It is a mildly severe form of this disorder and is similar to Type I. However, Osteogenesis Imperfecta Type 4 sufferers need crutches and braces to walk. Life expectancy is close to normal or completely normal.This types constitutes 5%.Sclera-normal. Fractures are seen at birth 30% and bony fragility is mild.

Subtypes: 2 4A with no dental lesion4B with dentinogenesis imperfecta

Osteogenesis Imperfecta and Eyes

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The reduced functioning of Type I collagen leads to the thinning of the sclera and consequent showing of the underlying veins through the whites of eyes.

Blue Sclera is one of the major symptoms of OI and helps in the diagnosis of the disorder.

These are also an important component of teeth, ligaments and whites of the eyes (sclera).

Blue sclera

Osteogenesis Imperfecta and Genetics

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This condition typically results from a genetic mutation. Medical research has been able to establish that the genetic defect causing OI runs in families.Type I of OI is a dominant inherited condition arising due to mutations on chromosome 17 in the COL1A1 gene, on chromosome 7 in the COL1A2 gene. This leads to reduced manufacture of normal collagen.This protein is a major constituent of the connective tissues located within the boneHence OI chiefly characterized by symptoms like multiple bone fractures, blue sclerae

Osteogenesis Imperfecta Diagnosis

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Physical examination of the sclera of the eyes is usually enough to diagnose this condition( bluish tinge). The condition is also diagnosed with the help of other methods, such asDNA blood testing for gene defects has an accuracy of 60-94%. Prenatal DNA mutation analysis can be performed in pregnancies with risk of OI to analyze uncultured chorionic villus cells.

Osteogenesis Imperfecta Diagnosis

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Prenatal ultrasonography: Most useful in evaluating OI types II and III by 2nd trimester. Findings include bowing, shortening and angulation of the long bones due to fractures and easy visualization of intracranial structures due to decreased ossification of the skull vault.3 important US criteria of specific diagnosis of OI-type-II: • a) FL greater than 3SD below the mean, • b)Demineralization of calvarium, • c) Multiple fracture within a single bone.

USGD, Osteogenesis imperfecta type I. Isolated femoral fracture with acute angulation (arrow). F, Osteogenesis imperfecta type IIA. Bowed femur with multiple discontinuities representing fractures.

OI Diagnosis-Plane radiography

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Obtain a radiographic skeletal survey after birth.Generalized osteoporosis is present In milder forms (Types I & IV)–Thin and gracile bones with thin cortices. Skull vault may be normal.In the more severe forms (types 2 and 3)-The bones are thick and short with multiple fractures and hyperplastic callus formation. The skull is osteopenic and multiple wormian bones are present. Multiple rib fractures may cause the bones to become broad and deformed.Platyspondyly and scoliosis are often present

Management Genetic counseling is necessary for couples who have a family history of Osteogenesis Imperfecta (OI) and are considering pregnancy.Physiotherapy, rehabilitation, and orthopaedic surgery are the mainstay of treatment for patients with osteogenesis imperfecta. In recent years, biphosphonate therapy has been used with success.

DIFFERENTIAL DIAGNOSIS

Battered baby syndrome:Idiopathic juvenile osteoporosis

Battered baby syndrome:

Alternative name Child abuse/Non accidental trauma.A young child, often under age 3, who has been repeatedly and severely neglected by caretakers. Battered children have signs of multiple episodes of trauma—e.g., subdural haematomas, fractures, bruises in various stages of healing—often with failure to thrive and chronic malnutrition.Fractures are usually metaphyseal. Multiple rib fractures, fracture of scapula, sternum, vertebra, tibia, metacarpal associated with intracranial injuries (subdural haematomas).Urinary hydroxypoline is not elevated.

Idiopathic juvenile osteoporosis:

Patient typically presents before puberty (8-13 years) and have osteoporosis (lumbar & thoracic vertebrae) that is progressive initially and later stabilizes. Vertebral compression fracture and characteristically metaphyseal fractures specially of lower limb bones occur.

Thank you

Osteogenesis imperfecta. Results from genetic mutations causing abnormalities in Type I collagen, and resulting in osteoporosis and low-trauma fractures (brittle bone disease). The different types vary in clinical presentation and severity. Frontal view of the femora in an infant showing reduced bone density and marked deformity due to multiple fractures.Lateral spinal radiograph in a 30-year-old man showing reduced bone density and end-plate fractures of all vertebrae. There is also evidence of a metallic pin in a previous hip fracture. Osteoporosis is much less common in men than in women, and more likely to be related to secondary causes, especially excess alcohol intake.

Radiological Features of Rickets

Radiological changes: Result from loss of orderly maturation and mineralization of cartilage cells at the growth plate. These changes predominate at the sites of bones which are growing most active. These sites are – around the knee, the wrist (particularly the ulna) , the anterior ends of the middle ribs, the proximal femur and the distal tibia, and depend on the age of the child. Changes at growth plate and cortex

Widening of physis (earliest change)/growth plate.loss of normal zone of provisional calcification adjacent to metaphysis.Irregular metaphyseal margins (Fraying)Splaying and cupping of the metaphysis.Indistinct cortex because of uncalcified subperiosteal osteoid.Some expansion in width of the metaphysis results in the swelling around the ends of the long bones .Rachitic rosary.( This expansion and cupping of the anterior ends of the ribs)Looser’s zone is uncommon on children