History

Fact Explanation
Multiple fractures, pathological fractures occur due to trivial trauma Osteogenesis imperfecta is a genetic disorder causing qualitative or quantitative defect in type 1 collagen which forms the bone matrix [1]. So the bones that are formed are dysplastic causing it to break even with minimal force. Bone fragility is severe in type II and III, moderate in IV and mild in type I. Type 1 is the most commonest form.[2] . In type II usually the child dies during or shortly after birth.
Short stature More prominent in type III and IV. [3] Micro fractures on the growth plates following minor trauma leads to disturbed enchondral ossification. Which ultimately results in disturbed growth. [4] Also the involvement of the spine is also an important factor for reduced truncal growth. it is due to multiple compression fractures of the vertebral bodies and progressing spinal deformities. this usually starts after 6 years [5]
Recurrent pulmonary infections Most of them have spinal deformities such as thoracic scoliosis reducing pulmonary function thereby increase pulmonary morbidity during adulthood.[6]
Presenile Hearing loss (progressively worsens) - Commonly conductive and mixed hearing loss seen. but also small percentage have sensorineural hearing loss. [7] Conductive hearing loss is due to either fixed stapedial foot plate or discontinuity of the ossicular chain which could either be due to fracture or aplasia of the crura of stapedius [7].
Limb deformities - Difficulty in ambulation Due to multiple fractures varies types of limb deformities are seen.
Lax joints Ligaments also contain type 1 collagen in their matrix [1]. so defective collagen leads to defective ligaments which cannot maintain the joint integrity.
Defective dentition- discolored teeth (blue gray/ yellow brown color), weak fragile teeth (seen in both primary and secondary teeth) [2] This is also known as Dentinogenesis imperfecta [8]. Dentin which is the calcified part of the tooth which gives the color to the teeth since the enamel is translucent. Dentin also consist type 1 collagen in its matrix which becomes weak in Osteogenesis imperfecta [1].
Cardiovascular abnormalities [9], [10] Congenital cardiac defects and acquired heart defects such as aortic root dilatation, aortic insufficiency, mitral valve prolapse are important extra skeletal manifestations of Osteogenesis imperfecta. [9] Since Osteogenesis imperfecta is a disorder of connective tissues with time manifests with cardiac lesions specially during adulthood.[10]
Renal manifestations [9]- urinary stone disease Renal stones formation and renal papillary calcification is also seen in childhood Osteogenesis imperfecta. [9]
Neurological manifestations- seizure disorder, headache,features of brain stem compression such as lower cranial nerve dysfunction, quadriparesis, ataxia, nystagmus etc [11] [12] Hydrocephalus, basilar invagination and cerebral atrophy are seen in Osteogenesis imperfecta. Basilar invagination leads to compression of the brain stem. Also skull fracture and seizure disorder may also lead to the neurological manifestations. [11][12]
Family history of Osteogenesis imperfecta It is an inherited genetic condition due to mutation of COL1A1, COL1A2 genes which are type I collagen forming protein coding genes resulting in quantitative or qualitative defects of type 1 collagen. 95% is inherited in an autosomal dominant fashion and the rest account to autosomal recessive pattern and new mutations. [13]. When a parent has the disease there is a 50% chance and if a sibling has the disease chance varies from 0-50% due to the mosaic pattern in parent. [14]
Easy bruising Is a common feature among OI patients. This could be due to increased capillary fragility, reduced platelet retention and reduced factor VIII. [15]
References
  1. KOCHER M S, SHAPIRO F. Osteogenesis imperfecta. Journal of the American academy of orthopaedic surgeons. July 1998, vol 6(4), 225 -236.
  2. OI Issues: Type I- Understanding th emildest form of osteogenesis imperfecta. National Institute of Health. January 2012. [viewed 04 April 2014]. Available from:
  3. LUND M Allan, MULLER J, SKOVBY F. Anthropometry of patients with osteogenesis imperfecta. Archives of Disease in Childhood. [online]. 1999, vol 80, 524-528. [viewed 27 March 2014]. Available from: doi:10.1136/adc.80.6.524
  4. SNOECKX A, VANHOENACKER F M, PARIZE P M. Popcorn calcifications in osteogenesis imperfecta. Images in Clinical radiology. JBR–BTR, 2008, vol 91, 176.
  5. DANIEL B R, DANIEL N C. The Spine and Surgical Treatment in Osteogenesis Imperfecta. Current orthopaedic practice - A review and research journal. September 1981, vol 159, 147-153.
  6. WIDMANN Roger F, BITAN Fabien D, et al. Spinal Deformity, Pulmonary Compromise, and Quality of Life in Osteogenesis Imperfecta. Spine. [online]. Lippincott Williams & Wilkins, Inc. 15 August 1999. vol 24 (16), 1673. [viewed 27 March 2014]. Available from: http://journals.lww.com/spinejournal/Abstract/1999/08150/Spinal_Deformity,_Pulmonary_Compromise,_and.8.aspx
  7. PEDERSEN U. Hearing Loss in Patients with Osteogenesis Imperfecta A Clinical and Audiological Study of 201 Patients. Scandinavian Audiology. [online]. 1984, Vol. 13(2), 67-74 [viewed 04 April 2014]. Available from: doi: 10.3109/01050398409043042.
  8. Dentinogenesis imperfecta. Genetics home referance. 31 March 2014. [viewed 04 April 2014]. Available from:
  9. VETTER U, MAIERHOFER B, MULLER M et al. Osteogenesis Imperfecta in childhood: cardiac and renal manifeststions. European Journal of Pediatrics. [online]. Springer-Verlag. December 1989, Vol 149(3), 184-187. [viewed 04 April 2014]. Available from: doi: 10.1007/BF01958277
  10. CRISCITIELLO M G, RONAN JR J A, BESTERMAN E M M, SCHOENWETTER W. Cardiovascular Abnormalities in Osteogenesis Imperfecta. Circulation. [online]. American Heart Association, Inc. 1965, vol 31, 255-262. [viewed 09 April 2014]. Available from: DOI : 10.1161/​01.CIR.31.2.255
  11. LAWRENCE R C, JOAN C M. Communicating hydrocephalus, basilar invagination, and other neurologic features in osteogenesis imperfecta. The official journal of the American academy of neurology. [online]. December 1993 vol, 43(12), 2603. [viewed 04 April 2014]. Available from: doi: 10.1212/WNL.43.12.2603.
  12. SAWIN P D, MENEZES A H. Basilar invagination in osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management. Journal of Neurosurgery. [online]. American association of Neurological surgeons. June 1997, Vol 86(6), 950-960. [viewed 04 April 2014]. Available from: doi: 10.3171/jns.1997.86.6.0950 .
  13. RENAUD A, AUCOURT J, WEILL J. Radiographic features of osteogenesis imperfecta. Insights into Imaging [online]. Springer. August 2013, vol 4(4), 417–429. [viewed 09 April 2014]. Available from: DOI: 10.1007/s13244-013-0258-4
  14. PEPIN M, ATKINSON M, STARMAN B J, BYERS P H. Strategies and outcomes of prenatal diagnosis for osteogenesis imperfecta: a review of biochemical and molecular studies completed in 129 pregnancies. Prenat Diagn 1997, vol17, 559–570.
  15. EVENSEN S A, MYHRE L, STORMORKEN H. Haemostatic studies in osteogenesis imperfecta. Scandinavian Journal of Haematology. [online]. John Wiley & Sons, Inc. August 1984, vol 33 (2), 177- 179. [viewed 09 April 2014]. Available from: DOI: 10.1111/j.1600-0609.1984.tb02393.x

Examination

Fact Explanation
Tinged sclera - blue/ violet It is due to an optical effect. Type1 collagen is a component of matrix of sclera as well [1]. Defective collagen synthesis causes thinning of sclera. So the darker uveal color is brought out when a light is going through sclera.
Anthropometry - reduced height, with relatively short trunk (short sitting height)and disproportionately increased head size [2] Since production of type 1 collagen is defective which is needed in the formation of bone matrix growth will also be affected. [2] Disproportionate short stature (Trunk length affected than limb length) is mainly due to the involvement of spine. Spine can have platyspondyly (radiographic characteristic where the vertebral bodies are flattened throughout the axial skeleton) or progressive shortening of axial skeleton can occur following spinal deformities [3]
Spinal deformities - kyphosis/ scoliosis Scoliosis is commonly seen among OI patients but secondary kyphosis can also occur due multiple compression fractures of vertebral bodies. [4]
Joint laxity The ligaments also contains type 1 collagen in their connective tissue matrix. In Osteogenesis imperfecta there is either qualitative or quantitative defect in production of type 1 collagen. this leads to defective ligament integrity. [1]
Hearing defects - conductive/ sensorineural/ mixed Conductive hearing loss is due to either fixed stapedial foot plate or discontinuity of the ossicular chain which could either be due to fracture or aplasia of the crura of stapedius [5]
Triangular face. A characteristic feature that occurs due to due to overdevelopment of the head and underdevelopment of the facial bones.
Macrocephaly Head circumference shows abnormal growth pattern which frequently cause macrocephaly [6]. Also due to basilar invagination there is compression of brain stem. This may lead to hydrocephalus as well. [6]
Barrel chest Because of the spinal deformities there is some amount of reduction of pulmonary functions which may lead to compensatory increase if the chest circumference.
CVS examination may reveal cardiovascular system abnormalities Since Osteogenesis imperfecta is a disorder of connective tissues with time manifests with cardiac lesions specially during adulthood [7] Abnormalities such as congenital heart disease such as aortic stenosis, ASD, tetralogy of Fallot and acquired defects such as Mitral valve prolapse, aortic insufficiency. [8]
Neurological manifestations - features of brain stem compression such as lower cranial nerve palsies, ataxia, nystagmus, Spinal compression, unexplained long tract signs. [3] [5] Neurological manifestations are caused by basilar invagination , skull fractures, cerebral atrophy etc. [6] [9]
Bruises Due to their tendency to bruise easily. Is a common feature among OI patients. This could be due to increased capillary fragility, reduced platelet retention and reduced factor VIII. [10]
References
  1. KOCHER M S, SHAPIRO F. Osteogenesis imperfecta. Journal of the American academy of orthopaedic surgeons. July 1998, vol 6(4), 225 -236.
  2. LUND M Allan, MULLER J, SKOVBY F. Anthropometry of patients with osteogenesis imperfecta. Archives of Disease in Childhood. [online]. 1999, vol 80, 524-528. [viewed 27 March 2014]. Available from: doi:10.1136/adc.80.6.524
  3. ENGELBERT R H H, GERVER W J M, BRESLAU- SIDERIUS L J, et al. Spinal complications in osteogenesis imperfecta 47 patients 1–16 years of age. Acta Orthopaedica. [online]. Informa Plc. 1998, Vol 69 (3), 283-286. [viewed 09 April 2014]. Available form: DOI: 10.3109/17453679809000931
  4. DANIEL B R, DANIEL N C. The Spine and Surgical Treatment in Osteogenesis Imperfecta. Current orthopaedic practice - A review and research journal. September 1981, vol 159, 147-153.
  5. PEDERSEN U. Hearing Loss in Patients with Osteogenesis Imperfecta A Clinical and Audiological Study of 201 Patients. Scandinavian Audiology. [online]. 1984, Vol. 13(2), 67-74 [viewed 04 April 2014]. Available from: doi: 10.3109/01050398409043042.
  6. LAWRENCE R C, JOAN C M. Communicating hydrocephalus, basilar invagination, and other neurologic features in osteogenesis imperfecta. The official journal of the American academy of neurology. [online]. December 1993 vol, 43(12), 2603. [viewed 04 April 2014]. Available from: doi: 10.1212/WNL.43.12.2603.
  7. CRISCITIELLO M G, RONAN JR J A, BESTERMAN E M M, SCHOENWETTER W. Cardiovascular Abnormalities in Osteogenesis Imperfecta. Circulation. [online]. American Heart Association, Inc. 1965, vol 31, 255-262. [viewed 09 April 2014]. Available from: DOI : 10.1161/​01.CIR.31.2.255
  8. VETTER U, MAIERHOFER B, MULLER M et al. Osteogenesis Imperfecta in childhood: cardiac and renal manifeststions. European Journal of Pediatrics. [online]. Springer-Verlag. December 1989, Vol 149(3), 184-187. [viewed 04 April 2014]. Available from: doi: 10.1007/BF01958277
  9. SAWIN P D, MENEZES A H. Basilar invagination in osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management. Journal of Neurosurgery. [online]. American association of Neurological surgeons. June 1997, Vol 86(6), 950-960. [viewed 04 April 2014]. Available from: doi: 10.3171/jns.1997.86.6.0950 .
  10. EVENSEN S A, MYHRE L, STORMORKEN H. Haemostatic studies in osteogenesis imperfecta. Scandinavian Journal of Haematology. [online]. John Wiley & Sons, Inc. August 1984, vol 33 (2), 177- 179. [viewed 09 April 2014]. Available from: DOI: 10.1111/j.1600-0609.1984.tb02393.x

Differential Diagnoses

Fact Explanation
Non accidental injury Mild OI can be confused with child abuse [1]. child abuse also can present with multiple fractures. but the fracture type can point out to child abuse. Also they may co exist.
Osteopenia of the prematurity Premature neonates have decreased bone mineralization, therefore are more prone to fractures in there infantile period. By one year their bone density normalizes. They commonly present between 6 - 12 weeks. [2]
Rickets This is due to Vitamin D deficiency and other disorders that cause defective mineralization leading to multiple fractures. This will cause bony deformities and specific radiographic changes. [3]
Scurvy (Vitamin C deficiency) It is due to deficiency if Vitamin C which is an important co factor in the collagen formation. thus presents with multiple fractures. but they characteristically have cutaneous bleeding manifestations due to capillary instability. [1]
Copper deficiency Copper is an important co factor for the enzyme Lysyl oxidase which oxidizes lysine and hydrolysine residues in Collagen synthesis. thus cause fragile bones [4]
Disuse osteopenia Seen in children who are paralyzed. With disuse the muscles becomes weaker and also there will be thinning of the bone leading to fragility. [5]
Vitamin A toxicity High dose Vitamin A can cause osteoporosis of bones. [6]
Menkes kinky hair syndrome It is syndrome due to copper deficiency, where they have characteristic kinked hair, growth retardation, neurological manifestations. [7]
Hypophosphatasia it is a fatal metabolic bone disease. Causing profound skeletal hypo mineralization.
Acute lymphoblastic leukemia Due to the disease and the chemotherapy drugs they develop osteopenia [8], thus multiple fractures which are usually vertebral .
Metabolic diseases that cause calcium wasting Causes diffuse osteopenia which lead to fragility fractures.
Chronic kidney disease In chronic kidney disease there is development of osteoporosis.
Cushing's disease Bones show osteoporotic changes in Cushing's, but there will be other cutaneous and systemic manifestations of glucocorticoid excess. [9]
Drugs such as Steroids , methotrexate, prostaglandins etc [2] Steroids cause secondary osteoporosis reducing the bone mineral density. Thereby cause pathological fractures. [9] prolonged use of prostaglandins increase bone resorption and also impairs fracture healing. [10]
Juvenile osteoporosis It could be either secondary to any other disease or medication or idiopathic [9]. osteogenesis imperfecta also can cause secondary osteoporosis since they don't attain normal bone mass. but in juvenile osteoporosis they do not develop extra skeletal manifestations like in osteogenesis imperfecta. [11]
Pyknodysostosis rare sclerosing bone disorder that has an autosomal dominant trait. It is characterized by short stature, brachycephaly, short and stubby fingers, open cranial sutures and fontanelle, and diffuse osteosclerosis, where multiple fractures of long bones and osteomyelitis of the jaw are frequent complications. [12]
Maffucci syndrome It is a genetic disorder of bones and skin. Affected children have multiple enchondromas commonly occurring in the limbs. Points of enchondromas are liable for fractures. Also affected children are short with bony deformities. [13]
Hajdu cheney syndorme Rare condition. Due to abnormal osteoblastic function, there is generalized osteoporosis. Leadin to multiple fractures, acro- osteolysis, absent frontal sinuses and joint laxity. [14]
Rhizomelic chondrodysplasia punctate Due to impaired skeletal development children with this disease has various skeletal deformities, respiratory problems and short stature. But these children has intellectual impairment and significant developmental delay in other areas as well. [15]
Osteopetrosis Also known as Albers-Schonberg disease, is due to defect in osteoclast bone resorption thereby increase bone thickness. But the bones formed are brittle, liable to frequent fractures. In OI osteopenia is the characteristic feature, thus radiographs will bring out the difference.
Mc Cune - Albright syndrome It is a fibrous dysplasia of the bones leading to multiple fractures and skeletal deformities. It also has multiple endocrine dysfunction. [16]
Hyperthyroidism Thyroid hormone affects bone mineralization. Excess of thyroid hormone causes osteopenia thus result in fractures [17]. But they will have other features of hyperthyroidism.
Juvenile DM Significant loss of bone mass occurs in juvenile as well as adult onset diabetes but it is not related to the severity of the disease. [18]
References
  1. Child Abuse Part I of III - Bruising and Fracture. University Park Legal nurse consulting. April 2011. [viewed 04 April 2014].Available from:
  2. CAROLE J. Evaluating Infants and Young Children With Multiple Fractures. Official Journal of American Academy of Paediatrics. [online]. American Academy of Pediatrics. 01 September 2006, Vol 118(3), 1299 -1303. [viewed 04 April 2014]. Available from: doi: 10.1542/peds.2006-1795.
  3. GEFTER W. Rickets Presenting As Multiple Fractures in Premature Infants on Hyperalimentation. Journal of Pediatric Orthopaedics. [online]. Lippincott Williams & Wilkins. August 1982, Vol 2(3), 340. [viewed 04 April 2014].
  4. HARRIS E D, RAYTON J K, BALTHROP J E, et al. Copper and the synthesis of elastin and collagen. [online]. Ciba Found Symp. 1980,79, 163-82. [viewed 04 April 2014]. available from: PMID: 6110524
  5. WAKLEY G K, PORTWOOD J S, TURNER R T. Disuse osteopenia is accompanied by downregulation of gene expression for bone proteins in growing rats. American Journal of Physiology - Endocrinology and Metabolism. 31 January 2006, vol 263, 1029 - 1034.
  6. MELHUS H, MICHAELSSON K, KINDMARK A, et al. Excessive Dietary Intake of Vitamin A Is Associated with Reduced Bone Mineral Density and Increased Risk for Hip Fracture. Annals of internal medicine. [online]. American College of Physicians. 15 November 1998, Vol 129(10), 770-778. [viewed 04 April 2014]. Available from: doi: 10.7326/0003-4819-129-10-199811150-00003
  7. Menkes syndrome. Genetics home reference. 31 March 2014. [viewed 04 April 2014]. Available from:
  8. VAN DER SLUIS I M, VAN DEN HEUVEL-EIBRINK M M, HAHLEN K et al. Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia.The Journal of Pediatrics. [online]. Elsevier Inc, August 2002, vol 141(2), 204- 210. [viewed 04 April 2014]. Available from: doi: 10.1067/mpd.2002.125728
  9. HAHN T J. Corticosteroid-Induced Osteopenia. Arch Intern Med. [online]. American Medical Association. 1978, vol 138(5), 882-885. [viewed 09 April 2014] Available from: doi:10.1001/archinte.1978.03630300050010.
  10. FRACON R N, TEOFILO J M, SATIN R B, LAMANO T. Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry. Journal of Oral Science . September 2008, Vol 50(3), 247-252.
  11. Juvenile osteoporosis. National Institutes of Health. January 2012. [viewed 04 April 2014]. Available from:
  12. RENUKA J, BATHI, MASUR VN. Pyknodysostosis – a report of two cases with a brief review of the literature. Pyknodysostosis – a report of two cases with a brief review of the literature. [online]. John Wiley & Sons, Inc. December 2000, vol 29(6), 439- 442. [viewed 04 April 2014]. Available from: DOI: 10.1034/j.1399-0020.2000.290609.x
  13. Maffucci syndrome. Genetics home reference. November 2010. [viewed 09 April 2014]. Available from:
  14. IWAYA T, TANIGUCHI K, WATANABE J, et al. Hajdu-Cheney syndrome. Archives of orthopaedic and traumatic surgery . Springer. December 1979, Vol 95(4), 293-302.
  15. Rhizomelic chondrodysplasia punctata. Genetics home reference. July 2010. [viewed 04 April 2014]. Available from:
  16. HAPPLE R. The McCune-Albright syndrome: a lethal gene surviving by mosaicism. Clinical Genetics. [online]. John Wiley & Sons, Inc. April 1986, vol 29 (4), 321- 324. [viewed 09 April 2014]. Available from: DOI: 10.1111/j.1399-0004.1986.tb01261.x
  17. TOH S H, CLAUNCH B C, BROWN P H. Effect of Hyperthyroidism and Its Treatment on Bone Mineral Content. Arch Intern Med. [online]. American Medical Association. 1985, vol 145(5), 883-886. [viewed 09 April 2014]. Available from: DOI: 10.1001/archinte.1985.00360050147025.
  18. LEVIN M E, BOISSEAU V C, AVIOLI L V. Effects of Diabetes Mellitus on Bone Mass in Juvenile and Adult-Onset Diabetes. The New England Journal of Medicine. [online]. Massachusetts Medical Society. 29 January 1976, vol 294, 242- 245. [viewed 09 April 2014]. Available from: DOI: 10.1056/NEJM197601292940502

Investigations - for Diagnosis

Fact Explanation
Antenatal ultrasonography (Trans abdominal / trans vaginal)- limb length abnormalities (eg. bowing), multiple fractures inutero, compressible cranium, transparent calvaria. micromelia etc Limb length abnormalities and multiple fractures in utero is seen in severe forms of Osteogenesis imperfecta from second trimester. Compressible and transparent cranium is seen due to low mineralization of the skull. But it is not diagnostic of Osteogenesis imperfecta [1] Non specific features such as intra uterine growth retardation, hydraminos can also be present. [2] milder forms may not be detected antenatally.
Prenatal Diagnosis done using chorionic villus sampling within the first trimester OI shows autosomal dominance inheritance but new mutations are common and also certain types show recessive pattern. When a parent has OI there is a 50% chance, and if a sibling has the chance varies from 0- 50% because of the parental mosaicism.[3]. Collagen synthesis analysis could be done using the cultured chorionic villus sampling which could only be done in type II,III,IV [4]. Mutation analysis could be done using the DNA obtained in chorionic villus sampling or amniocentesis. [4]. This should be in families who already have or had a child/ parent with osteogenesis imperfecta [1].
A full skeletal survey by plain radiographs. After birth at different stages of life its mostly diagnosed with clinical features and radiological examination. conventional radiography is the mainstay of diagnosing. More sophisticated investigations such as DNA tests are needed when the diagnosis cannot be made. [5]
X ray - skull: shows wormian bones, platybasia, enlargement of frontal and mastoid sinuses. Significant number of Wormian bones are seen in most severe form of Osteogenesis imperfecta [6]. Platybasia which is abnormal flattening of the base of skull and basilar impression which is seen in CT are seen Osteogenesis imperfecta tarda which is the less severe form of the disease. [7]
Xray chest- fractured and beaded ribs, pectus carinatum, barrel chest Multiple rib fractures and repeated healing by callus formation produces fractured and continuously beaded ribs. [8]. Since there is chronic pulmonary insufficiency to increase the respiratory capacity the chest becomes barrel shaped.
Pelvis x ray - Shepherd's crook deformity of the femurs, multiple fractures and dislocations, narrow pelvis, protrusio acetebuli Shepherd's crook deformity - coxa varus angulation of the proximal femur - occurs due to repeated fractures of proximal femur [9] Due to bone fragility
X ray long bones- multiple fractures and excessive callus formation, popcorn bones, irregular and partially or completely absent growth plates in children Popcorn calcifications are multiple small radiolucent calcifications with sclerotic margins in epiphysis and metaphysis of long bones. Seen always around abnormal growth plates. They are detached fragments of growth plates following minor trauma which leads to micro fractures of the growth plates. [2]
spinal deformities such as scoliosis/ kyphosis,Vertebral compression fractures, cod fish vertebrae, platyspondyly Commonly progressive scoliosis is seen among OI patients but secondary kyphosis can also occur due to multiple compression fractures [10]. Severity of the curvature is dependent on the severity of the disease and age. soft brittle bones of the vertebrae are prone to compression fractures. laxity of the vertebral ligaments also plays an important role in instability of the spine. Pressure on the normal nucleus pulposes cause vertebrae to become biconcave in shape thus attain the cod fish vertebrae. platyspondyly is the flattened vertebral bodies throughout the axial skeleton which is seen in the radiograph. [10]
Skin biopsy - collagen synthesis analysis. Fibroblasts could be cultured and collagen synthesis could be analyzed with various methods. In OI it may show either quantitative defect or qualitative defect of type 1 procollagen [4]. Quantitative defect is seen in less severe Osteogenesis imperfecta, and qualitative defect is seen in severe Osteogenesis imperfecta [11]
Bone densitomery - DEXA scan Shows decreased bone mineral density. Osteopenia is a characteristic feature of any type of OI. Can use to diagnose and monitor progression. [5]
CT / MRI of brain - basilar invagination, hydrocephalus, ventral brain stem compression, syringomyelia/ syringobulbia can be seen rarely [12]
Metabolic screen The results are usually normal. This done to exclude other metabolic diseases.
Genetic testing (mutation analysis) - to identify specific gene defects Genetic testing is done to identified mutation in COL1A1, COL1A2 which encodes type 1 procollagen chains. >90% of the patients have been estimated to have mutations in those two genes[13]. But they do not cause type V, VI and VII Osteogenesis imperfecta. [4] Warranted only if diagnosis cannot be made by the usual History, examination, radiographs. Accuracy is high.
Cervical spine - basilar invagination (it is a craniocervical junction abnormality. The tip of odontoid process projects above the foramen magnum into the cranium ) It is congenital or acquired. Where there is upward migration of the cervical spine. It is associated with platybasia where the base of skull is soft and flat and the laxity of ligaments in OI also contribute. [14] This leads to stenosis of foramen magnum and its associated sequelae explained in examination.
Low dose CT with 3D reconstruction of the whole fetal skeleton. Done when termination of pregnancy is considered but the diagnosis is in doubt after USS. Done after 26 weeks. Will give a definite diagnosis. [2]
References
  1. BERGE L N, MARTON V,TRANEBJAERG L, et al. Prenatal diagnosis of osteogenesis imperfecta. Acta Obstetricia et Gynecologica Scandinavica. [online]. Informa Plc. 1995, vol 74(4), 321-323. [viewed 09 April 2014]. Available from: DOI: 10.3109/00016349509024458
  2. SNOECKX A, VANHOENACKER F M, PARIZE P M. Popcorn calcifications in osteogenesis imperfecta. Images in Clinical radiology. JBR–BTR, 2008, vol 91, 176.
  3. PEPIN M, ATKINSON M, STARMAN B J, BYERS P H. Strategies and outcomes of prenatal diagnosis for osteogenesis imperfecta: a review of biochemical and molecular studies completed in 129 pregnancies. Prenat Diagn 1997, vol17, 559–570.
  4. BYERS P H, KRAKOW D, NUNES M E, PEPIN M. Genetic evaluation of suspected osteogenesis imperfecta (OI). Genetics in Medicine. [online]. American College of Medical Genetics and Genomics. 2006, 8, 383–388. [viewed 09 April 2014]. Available from: DOI: 10.1097/01.gim.0000223557.54670.aa
  5. RENAUD A, AUCOURT J, WEILL J. Radiographic features of osteogenesis imperfecta. Insights into Imaging [online]. Springer. August 2013, vol 4(4), 417–429. [viewed 09 April 2014]. Available from: DOI: 10.1007/s13244-013-0258-4
  6. SEMLER O, CHEUNG M S, et al. Wormian bones in osteogenesis imperfecta: correlation to clinical findings and genotype. American journal of Medical Genetics part A. [online]. NCBI, July 2010, vol 152A(7), 1681-7. [viewed 1 April 2014]. Available from: doi: 10.1002/ajmg.a.33448
  7. FRANK E, BERGER T, TEW JR J M. Basilar impression and platybasia in osteogenesis imperfecta tarda. Surgical Neurology. [Online]. Elsevier Inc. February 1982, vol 17(2), 116- 119. [viewed 09 April 2014]. Available from: DOI: http://dx.doi.org/10.1016/S0090-3019(82)80033-5
  8. SILLENCE D O, BARLOW K K, GARBER A P, et al. Osteogenesis imperfecta type II delineation of the phenotype with reference to genetic heterogeneity. American Journal of Medical Genetics. [online]. John Wiley & Sons, Inc. February 1984, vol 17(2), 407- 423. [viewed 09 April 2014]. Available from: DOI: 10.1002/ajmg.1320170204
  9. LIVESLY P J, MCALLISTER J C R, CATTERRALL A. The treatment of progressive coxa vara in children with bone softening disorders. International Orthopaedics. [online]. October 1994, Vol 18(5), 310-312. [viewed 09 April 2014]. Available form: DOI: 10.1007/BF00180233
  10. DANIEL B R, DANIEL N C. The Spine and Surgical Treatment in Osteogenesis Imperfecta. Current orthopaedic practice - A review and research journal. September 1981, vol 159, 147-153.
  11. FRANCIS M J O, SMITH R, BAUZE R J. Instability of Polymeric Skin Collagen in Osteogenesis Imperfecta. British Medical Journal. [online]. 9 March 1974, vol 1(5905), 421–424. [viewed 09 April 2014]. Available from: PMCID: PMC1633248
  12. SAWIN P D, MENEZES A H. Basilar invagination in osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management. Journal of Neurosurgery. [online]. American association of Neurological surgeons. June 1997, Vol 86(6), 950-960. [viewed 04 April 2014]. Available from: doi: 10.3171/jns.1997.86.6.0950 .
  13. KORKKO J, ALA-KOKKO L, DE PAEPE A, et al. Analysis of the COL1A1 and COL1A2 Genes by PCR Amplification and Scanning by Conformation-Sensitive Gel Electrophoresis Identifies Only COL1A1 Mutations in 15 Patients with Osteogenesis Imperfecta Type I: Identification of Common Sequences of Null-Allele Mutations. The American Journal of human Genetics. [online]. Elsevier Inc. January 1998. vol 61(1), 98- 110. [ viewed 09 April 2014]. Available from: DOI: http://dx.doi.org/10.1086/301689
  14. DIXON A. Basilar invagination. Radiopaedia.org. [viewed 09 April 2014]. Available from:

Management - General Measures

Fact Explanation
Regular exercise To maintain good muscle power.
Balanced diet To maintain adequate BMI
Avoid steroid medication Patient/ parent should inform any doctor they consult regarding their condition, so that steroids can be avoided which causes secondary osteopenia.
Physiotherapy to improve muscle strength and also to reduce contractures [1]
Pain management Multiple fractures and deformities can cause pain to the child which should be ideally managed to give a better quality of life.
Orthosis to improve mobility of the patient. Fractures and deformities may limit the child's mobility and other functions. proper orthotic support can improve the functional status of the child thus prevent disuse muscle weakness and disuse osteopenia [1]
Genetic counseling to parents Since it is an inherited condition as explained in the history genetic counseling is needed to parent sin planning the next pregnancy and to make an antenatal diagnosis using the methods explained in investigations and do the needful. When a sibling has the disease chance in next child varies from 0-50% due to the mosaic pattern in parent [2]
References
  1. LEONID Z, FRANCOIS F, FRANCIS G H. Modern Approach to children with Osteogenesis imperfecta. Journal of Pediatric Orthopaedics B. March 2003, vol 12(2), 77-87.
  2. PEPIN M, ATKINSON M, STARMAN B J, BYERS P H. Strategies and outcomes of prenatal diagnosis for osteogenesis imperfecta: a review of biochemical and molecular studies completed in 129 pregnancies. Prenat Diagn 1997, vol17, 559–570.

Management - Specific Treatments

Fact Explanation
No curative treatment is only option is symptomatic treatment. A multidisciplinary team approach is needed for proper management. Since it is a genetic disease there is no specific treatment to cure this disease. type II disease lethal in utero or just after birth. Type III disease is severe which leads to death mostly due to respiratory complications.
Bisphosphonates - Cyclical Intravenous pamidronate. Bisphosphonates are pyrophosphate analogue which binds to hydroxy apatite in bones thereby inhibit osteoclast mediated bone resorption. This leads to increase in bone mineral density thus reduce the risk of fractures. [1]. Though their benefits and short term safety are well explained long term effects are not well studied [2]
Proper management of fracture - eg. intra medullary rodding of long bones [3] Early proper management of fracture improves healing and reduces deformities.
surgical management of basilar herniation and . Basilar herniation as explained in the investigation can cause medullary compressive symptoms which could be corrected by surgery and improve the child's condition [4]
Correction of scoliosis Correction will be difficult because of their bone fragility. curving of spine starts around 5-6 years and progress rapidly. Early bracing, though effective way to control scoliosis/ kyphosis, in OI patients with soft rib cage may compress the chest wall increasing the pulmonary compromise. [5]
Proper dental management Dentinogenesis imperfecta is part of the disease in certain types of disease. they have poor dentin development. Thus cause frequent breaking of the teeth. so they need to protect as well as manage any teeth fractures. May need implantation of the teeth as well.
Early identification and treatment of respiratory comlications Respiratory disease is a common morbidity and a common cause of death.
References
  1. GLORIEUX F H, BISHOP N J, PLOTKIN H et al. Cyclic Administration of Pamidronate in Children with Severe Osteogenesis Imperfecta. The New England Journal of Medicne. [online]. Massachusetts Medical Society. 1 October 1998, 339, 947-952. [viewed 04 April 2014]. Available from: DOI: 10.1056/NEJM199810013391402
  2. CHEUNG MS, GLORIEUX F H. Osteogenesis Imperfecta: Update on presentation and management. Reviews in Endocrine and Metabolic Disorders [online]. Springer US. June 2008, Vol 9(2),153-160. [viewed 04 April 2014]. Available from: doi: 10.1007/s11154-008-9074-4
  3. LEONID Z, FRANCOIS F, FRANCIS G H. Modern Approach to children with Osteogenesis imperfecta. Journal of Pediatric Orthopaedics B. March 2003, vol 12(2), 77-87.
  4. SAWIN P D, MENEZES A H. Basilar invagination in osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management. Journal of Neurosurgery. [online]. American association of Neurological surgeons. June 1997, Vol 86(6), 950-960. [viewed 04 April 2014]. Available from: doi: 10.3171/jns.1997.86.6.0950 .
  5. BENSON D R, NEWMAN D C. The spine and surgical treatment in osteogenesis imperfecta. Clin Orthop Relat Res. [online]. 1981 Sep, 159, 147-53. [viewed 09 April 2014]. Available from: PMID: 7285452