summary Osteogenesis Imperfecta is a common congenital disorder caused by a mutation in COL1A1 or COL1A2 genes resulting in abnormal collagen cross-linking and overall decrease in type 1 collagen. Patients present with fragility fractures, scoliosis, hearing loss, and cardiovascular abnormalities. Diagnosis is made based on family history associated with typical radiographic and clinical features. No commercially available diagnostic test exists due to the variety of genetic mutations. Treatment is a multidisciplinary approach for fracture prevention with bisphosphonates, fracture management when present, and realignment osteotomies for long bone deformities. Etiology Pathophysiology can result from decreased collagen secretion production of abnormal collagen leads to insufficient osteoid production physeal osteoblasts cannot form sufficient osteoid periosteal osteoblasts cannot form sufficient osteoid and therefore cannot remodel normally Genetics 90% have an identifiable genetic mutation COL 1A1 and COL 1A2 causes abnormal collagen cross-linking via a glycine substitution in the procollagen molecule autosomal dominant and autosomal recessive forms milder autosomal dominant forms (Types I and IV) severe autosomal dominant forms (Types II and III) autosomal recessive forms (Type VI, VII) CRTAP and LEPRE1 genes associated with severe, lethal forms of OI not associated with primary structural defect of type I collagen Orthopaedic manifestations bone fragility and fractures fractures heal in normal fashion initially but the bone does not remodel can lead to progressive bowing ligamentous laxity short stature scoliosis codfish vertebrae (compression fx) basilar invagination olecranon apophyseal avulsion fx coxa vara (10%) congenital anterolateral radial head dislocations Non-Orthopaedic manifestations blue sclera dysmorphic, triangle shaped facies hearing loss 50% of adults with OI may be conductive, sensorial and mixed brownish opalescent teeth (dentinogenesis imperfecta) alteration in dentin brown/blue teeth, soft, translucent, prone to cavities affects primary teeth > secondary teeth wormian skull bones (puzzle piece intrasutural skull bones) hypermetabolism increased risk of malignant hyperthermia hyperhidrosis, tachycardia, tachypnoea, heat intolerance thin skin prone to subcutaneous hemorrhage cardiovascular mitral valve prolapse aortic regurgitation Anatomy Type I collagen is the most important structural protein of bone, skin, tendon, dentin, sclera triple helix structure two alpha-1 chains coded by genes COL1A1 one alpha-2 chain coded by gene COL1A2 triple helix structure is possible because of glycine at every 3rd amino acid residue genetic mutations alter triple helix by substitution of glycine with another amino acid Classification Sillence originally classified into four types however most likely a continuum of disease additional types have been added 90% of patients can be grouped into the Sillence Type I and IV Sillence Classification of Osteogenesis Imperfecta (simplified) Type Inheritance Sclera Features Type I Autosomal dominant Quantitative disorder in collagen Blue Mildest form. Presents at preschool age (tarda). Hearing deficit in 50% Divided into type A and B based on tooth involvement Type II Autosomal dominant Qualitative disorder in collagen Blue Lethal in perinatal period Type III Autosomal dominant Qualitative disorder in collagen Normal Most severe survivable form Fractures at birth. Progressively short stature. Type IV Autosomal dominant Qualitative disorder in collagen Normal Moderate severity. Bowing bones and vertebral fractures are common. Hearing normal. Divided into type A and B based on tooth involvement Sillence Classification modification (Types V-VII added) These 3 types of OI have no Type I collagen mutation but have abnormal bone on microscopy and a similar phenotype Type V Congenital anterolateral radial head dislocation Hypertrophic callus after a fracture Ossification of IOM between radius and ulna and tibia and fibula Autosomal Dominant Type VI Moderate severity Similar to type IV Autosomal recessive Type VII Associated with rhizomelia and coxa vara Autosomal recessive Presentation Symptoms mild cases multiple fractures during childhood severe cases present with fractures at birth and can be fatal number of fractures typically decreases as patient ages and usually stops after puberty basilar invagination presents with apnea, altered consciousness, ataxia, or myelopathy usually in third or fourth decade of life, but can be as early as teenage years Physical exam multiple fractures leads to saber shin appearance of tibia bowing of long bones trendelenburg gait if coxa vara present Imaging Radiographs thin cortices generalized osteopenia saber shins skull radiographs reveal wormian bones coxa vara Evaluation Labroratory mildly elevated ALP Histology increased diameter of haversion canals and osteocyte lacunae replicated cement lines increased number of osteoblasts and osteoclasts decreased number of trabeculae decreased cortical thickness Diagnosis diagnosis is based on family history associated with typical radiographic and clinical features Labs no commercially available diagnostic test due to variety of genetic mutations laboratory values are typically within normal range possible methods diagnosis include skull radiographs to look for wormian bones fibroblast culturing to analyze type I collagen (positive in 80% of type IV) can be used for confirmation of diagnosis in equivocal cases biopsy collagen analysis of a punch biopsy iliac crest biopsy which shows a decrease in cortical widths and cancellous bone volume, with increased bone remodeling. Treatment of Fractures Fracture prevention early bracing indicated to decrease deformity and lessen fractures bisphosphonates indicated in most cases of OI to reduce fracture rate, pain, improve ambulation marked improvement in pain at 1-6wk after initiation inhibits osteoclasts increases cortical diameter 88% increases cancellous bone volume 46% does not affect development of scoliosis chronic use causes horizontal metaphyseal bands seen on radiographs growth arrest lines maintain bisphosphonate-free period around the time of IM rodding interferes with osteotomy healing >> fracture healing growth hormone bone marrow transplantation has been used with some success Fracture treatment nonoperative observation indications indicated if child is <2 years (treat as child without OI) operative fixation with telescoping rods indications consider in patients > 2 years allow continued growth fixation with load sharing device indications consider in patients > 2 years fracture with deformity beyond accepted tolerances after closed reduction Treatment of Long Bone Bowing Deformities Operative realignment osteotomy with rod fixation (Sofield-Miller procedure) indications severe deformity to reduce fracture rates techniques include nontelescopic devices (Rush rods, Williams rods) telescopic devices (Sheffield rod, Bailey-Dubow rod, Fassier-Duval rod) Treatment of Scoliosis Vital capacity drops to 40% of expected for a 60° curve Nonoperative observation indications if curve is <45 ° bracing is ineffective and not recommended because of fragility of ribs Operative posterior spinal fusion indications for curves > 45 ° in mild forms and > 35 ° in severe forms technique challenging due to fragility of bones use allograft instead of iliac crest autograft due to paucity of bone ASF only indicated in very young children to prevent crankshaft associated with a large blood loss Treatment of Basilar Invagination Operative decompression and posterior fusion indications radiographic features of invagination and cord compression with physical exam findings of myelopathy techniques resection of bony compression via transoral approach
QUESTIONS 1 of 21 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (SBQ13PE.108) A 14-year-old girl with osteogenesis imperfecta (Type I) falls and sustains a both-bone forearm fracture. The extremity is closed and neurovascularly intact. Closed reduction and casting are performed as seen in Figures A and B. What is the next best step in the management of this injury? QID: 5339 FIGURES: A B Type & Select Correct Answer 1 Continued casting with repeat radiographs in 2 weeks 15% (296/1976) 2 Realignment osteotomy and intramedullary rod fixation 3% (59/1976) 3 Realignment osteotomy and plate fixation 2% (44/1976) 4 Intramedullary rod fixation 50% (981/1976) 5 Plate fixation 30% (585/1976) L 4 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review Tested Concept Review Full Topic (SBQ13PE.61) Mutations in genes COL1A1/COL1A2 are responsible for the clinical manifestations of: QID: 5151 Type & Select Correct Answer 1 Marfan's syndrome 6% (229/4109) 2 Osteopetrosis 1% (54/4109) 3 Osteogenesis imperfecta 85% (3500/4109) 4 Achondroplasia 4% (151/4109) 5 Multiple Epiphyseal Dysplasia 4% (158/4109) L 2 Question Complexity A Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ11.207) A 12-year-old girl has been diagnosed with a severe form of osteogenesis imperfecta that has resulted in thin bones and multiple fractures. She now presents for follow-up of scoliosis which was noticed by her mother 1 year ago. She has no back pain and is neurologically intact. Radiographs show a 42-degree right thoracic curve, which has increased from 31-degree from her previous radiographs taken 9 months earlier. What is the most appropriate management for her spinal deformity? QID: 3630 Type & Select Correct Answer 1 Observation alone with serial radiographic and clinical monitoring. 5% (141/2830) 2 Posterior spinal fusion with instrumentation 62% (1767/2830) 3 Anterior spinal fusion with instrumentation 3% (74/2830) 4 Fixation with telescoping rods 6% (166/2830) 5 Custom-molded bracing with serial radiographic and clinical monitoring. 24% (666/2830) L 3 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (OBQ11.216) A 10-year-old girl has bilateral knee radiographs as shown in Figure A. Which of the following conditions is most likely present? QID: 3639 FIGURES: A Type & Select Correct Answer 1 Osteogenesis imperfecta (OI) 70% (2048/2923) 2 Ellis-van Creveld (EVC) syndrome/chondroectodermal dysplasia 15% (449/2923) 3 Marfan syndrome 2% (70/2923) 4 Caffey disease 9% (274/2923) 5 Juvenile idiopathic arthritis (JIA) 2% (71/2923) L 2 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ10.265) Which of the following pediatric congenital disorders is caused by a glycine substitution in the procollagen molecule? QID: 3316 Type & Select Correct Answer 1 Scurvy 7% (179/2733) 2 Osteogenesis imperfecta 81% (2210/2733) 3 Fibrous dysplasia 6% (151/2733) 4 Diastrophic dysplasia 4% (108/2733) 5 Ochronosis (alkaptonuria) 3% (73/2733) L 2 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (OBQ09.68) Type I collagen defects are responsible for the clinical manifestations of osteogenesis imperfecta. Mutation of what gene or genes are most responsible for this? QID: 2881 Type & Select Correct Answer 1 FGFR3 3% (67/2297) 2 FGFR2 2% (57/2297) 3 COMP 2% (36/2297) 4 COL1A1/COL1A2 91% (2094/2297) 5 Fibrillin 1% (34/2297) L 1 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ08.263) An adolescent male with a known genetic mutation of COL1A1 presents to the emergency department with symptoms of unsteady gait and difficulty with buttoning his shirt. On physical exam, when the patient holds his fingers extended and adducted, the small finger spontaneously abducts. Snapping of the patient's distal phalanx of the middle finger leads to spontaneous flexion of the other fingers. What is the most likely cause of the patient's symptoms? QID: 649 Type & Select Correct Answer 1 Basilar invagination 53% (955/1803) 2 C6 cervical disc foraminal herniation 6% (114/1803) 3 Atlantoaxial instability 34% (621/1803) 4 Ossification of the posterior longitudinal ligament (OPLL) 5% (96/1803) 5 Epidural abscess 1% (10/1803) L 4 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic This is an AAOS Self Assessment Exam (SAE) question. Orthobullets was not involved in the editorial process and does not have the ability to alter the question. If you prefer to hide SAE questions, simply turn them off in your Learning Goals. (SAE07PE.46) In children with moderate to severe osteogenesis imperfecta (OI), intravenous pamidronate therapy has been shown to increase the thickness of cortical bone. This occurs primarily as a consequence of QID: 6106 Type & Select Correct Answer 1 increased bone turnover in the cortical area. 2% (8/454) 2 inhibition of osteoclast-mediated bone resorption. 89% (404/454) 3 improved mineralization of cortical bone. 5% (22/454) 4 improved osteoblast organic matrix production. 3% (13/454) 5 improved organization of collagen matrix. 1% (4/454) L 1 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (OBQ06.205) A mutation in the COL1A1 and COL1A2 genes is associated with all of the following manifestations EXCEPT: QID: 216 Type & Select Correct Answer 1 Basilar invagination 6% (133/2076) 2 Webbed neck 68% (1417/2076) 3 Olecranon apophyseal avulsion fractures 11% (233/2076) 4 Scoliosis 4% (91/2076) 5 Discoloration of sclerae 9% (183/2076) L 3 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review Tested Concept Review Full Topic (OBQ05.220) A 12-year-old girl presents with a history of numerous long bone fractures in the past. Examination reveals normal-appearing sclera, and the dentin abnormality shown in Figure A. A radiograph of her lower extremities is shown in Figure B. The patient’s disorder is the result of which of the following? QID: 1106 FIGURES: A B Type & Select Correct Answer 1 Vitamin D deficiency 12% (137/1174) 2 Abnormal osteoclast function 2% (25/1174) 3 Qualitative defect of type I collagen synthesis 77% (909/1174) 4 Mutated fibroblast growth factor receptor 3% (30/1174) 5 Defective N-Ac-Gal-6 sulfate sulfatase enzyme 5% (62/1174) L 2 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Review Tested Concept Review Full Topic (OBQ04.263) A child has a genetic disorder of the COL1A1 gene resulting in a decreased production of functional type I collagen. Which of the following radiographs is MOST consistent with his condition? QID: 1368 FIGURES: A B C D E Type & Select Correct Answer 1 Figure A 7% (116/1634) 2 Figure B 5% (78/1634) 3 Figure C 4% (68/1634) 4 Figure D 79% (1283/1634) 5 Figure E 5% (79/1634) L 2 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review Tested Concept Review Full Topic
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Acute on Chronic Olecranon Fracture in 18F (C1133) Jan Szatkowski Pediatrics - Osteogenesis Imperfecta E 1/20/2012 131 2 7