{"id":70,"date":"2021-07-25T05:51:43","date_gmt":"2021-07-25T05:51:43","guid":{"rendered":"https:\/\/medinaz.com\/blog\/?p=70"},"modified":"2022-08-12T08:59:06","modified_gmt":"2022-08-12T08:59:06","slug":"osteogenesis-imperfecta","status":"publish","type":"post","link":"https:\/\/medinaz.com\/blog\/2021\/07\/25\/osteogenesis-imperfecta\/","title":{"rendered":"Osteogenesis Imperfecta – Medinaz HighYield Notes"},"content":{"rendered":"\n

Osteogenesis imperfecta <\/strong>also called \u201cBrittle Bone Disease\u201d <\/strong>comprises a heterogeneous group of heritable disorders. The disorders are frequently associated with blue sclerae, dental abnormalities (dentinogenesis imperfecta), progressive hearing loss, and a positive family history.<\/p>\n\n\n\n

Most patients have mutations in one of the two genes coding for Type I collagen<\/em><\/strong><\/p>\n\n\n\n

More than 90% of cases exhibit an autosomal dominant<\/em><\/strong> inheritance<\/p>\n\n\n\n

Commonly mutated genes are COL1A1 <\/strong><\/em>and COL1A2<\/strong><\/em><\/p>\n\n\n\n

This condition represents one of the most common heritable bone diseases, with a worldwide prevalence of approximately 6 to 7 per 100,000 population.<\/p>\n\n\n\n

\"Osteogenesis<\/figure>\n\n\n\n\n\n\n\n

<\/p>\n\n\n\n

Classification of Osteogenesis Imperfecta<\/strong><\/p>\n\n\n\n

Phenotype<\/td>Type<\/td>Typical features<\/td>Inheritance<\/td>Gene\/Protein defect<\/td>Protein defect<\/td><\/tr>
Non-deforming form  <\/td>OI type 1  <\/td>Mild to moderate bone fragility, normal or near normal stature, in most, blue sclerae, normal dentition in most hearing loss in ~50%.  <\/td>AD<\/td>COL1A1 COL1A2<\/em><\/strong>  <\/td>Collagen I haploinsufficiency  <\/td><\/tr>
Perinatally lethal form  <\/td>OI type 2  <\/td>Extreme bone fragility, short stature, long bone bowing  <\/td>AD AR  <\/td>COL1A1 COL1A2 <\/em><\/strong>CRTAP LEPRE1\/<\/em>P3H1 PPIB\/<\/em>CYPB  <\/td>Collagen I structural mutations Collagen post-translational modification and folding machinery  <\/td><\/tr>
Progressively deforming OI  <\/td>OI type 3  <\/td>Moderate to severe bone deformity, blue sclerae at birth, hearing loss and abnormal dentition common.  <\/td>AD AR  <\/td>COL1A1<\/em><\/strong> COL1A2<\/em><\/strong> CRTAP<\/em> LEPRE1\/<\/em>P3H1 PPIB\/<\/em>CYPB FKBP10\/<\/em>FKBP65 PLOD2<\/em>\/ LH2 SERPINH1\/<\/em>HSP47 CREB3L1<\/em>\/OASIS SEC24D<\/em> BMP1<\/em>\u2028<\/em><\/em> WNT1 <\/em><\/em> SERPINF1\/<\/em>PEDF TMEM38B\/<\/em>TRIC-B SP7\/<\/em>OSX  <\/td>Collagen I structural mutations Collagen post-translational modification and folding machinery Protein folding\/endoplasmic reticulum stress sensor COPII vesicle component collagen secretion Proteolytic removal of procollagen N-propeptide\u2028Wnt cell signaling pathway Signaling and collagen binding protein, important for mineralization Endoplasmic reticulum cation channel. Calcium homoestasis\/collagen synthesis Transcription factor, bone formation<\/td><\/tr>
Common Variable OI with normal sclerae<\/td>OI type 4<\/td>Mild to moderate, bone fragility, normal sclerae, variable dentition, hearing loss in <10%.  <\/td>AD AR  <\/td>COL1A1<\/em><\/strong>\u2028<\/em><\/strong><\/em><\/strong> COL1A2<\/em><\/strong>\u2028<\/em><\/strong><\/em><\/strong> WNT1<\/em>\u2028<\/em><\/em> CRTAP FKBP10\/<\/em>FKBP65 PPIB\/<\/em>CYPB SERPINF1\/<\/em>PEDF SPARC<\/em><\/em> SP7\/<\/em>OSX <\/em>  <\/td>Collagen I structural mutations Wnt cell signaling pathway Collagen post-translational modification and folding machinery Signaling and collagen binding protein, important for mineralization Collagen binding\/extracellular matrix assembly Transcription factor, bone formation  <\/td><\/tr>
OI with calcification of the interosseous membranes<\/td>OI type 5  <\/td>Calcification of the interosseous membranes\u2028in forearm and legs and\/or hypertrophic callus. Variable bone deformity, normal sclerae and dentition.  <\/td>AD<\/td>IFITM5<\/em>  <\/td>Transcription factor, bone formation<\/td><\/tr>
Bruck syndrome type 1<\/td>BRKS1<\/td>Contractures with pterygia, fractures in infancy or early childhood, postnatal short stature, severe limb deformity, and progressive scoliosis<\/td>AR<\/td>FKBP10\/<\/em>FKBP65  <\/td>Collagen folding machinery<\/td><\/tr>
Bruck syndrome type 2<\/td>BRKS2<\/td>As for Bruck syndrome type 1  <\/td>AR<\/td>PLOD2\/<\/em>LH2  <\/td>Collagen post-translational modification of lysine<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

<\/p>\n\n\n\n

Incidence<\/strong><\/p>\n\n\n\n

<\/p>\n\n\n\n

Osteogenesis imperfecta TYPE I<\/strong> – 1 in 15,000\u201320,000 births<\/p>\n\n\n\n

Osteogenesis imperfecta TYPE II <\/strong>– 1 in 60,000<\/p>\n\n\n\n

Clinical features<\/strong><\/p>\n\n\n\n

Skeletal Defect:<\/strong><\/p>\n\n\n\n

Type I OI \u2013<\/strong><\/p>\n\n\n\n