IllnessOsteogenesis imperfecta, differential diagnosis

NGS +

[Sanger]

Osteogenesis imperfecta (OI) comprises a heterogeneous group of genetic disorders with increased bone fragility, low bone mass and susceptibility to fractures of varying degrees of severity, sometimes even prenatally. At least 20 forms of OI are recognised and several types are distinguished by their symptoms, although characteristic features also overlap. Increasingly, mutated genes are used to define rarer OI forms. Type I is the mildest form and is known as classical non-deforming OI with blue sclerae. Type II (also known as perinatal lethal) is the most severe form. Other forms, including types III (progressively deforming OI) and IV (frequent variable OI with normal sclerae), have symptoms that lie between the above extremes. In addition to all classic hereditary forms (with variable expressivity), some of the most severe OI forms also or only after sporadic new mutations. Mutations in the COL1A1 (5-70%) and COL1A2 (5-30%) genes make up by far the largest proportion of OI causes. The diagnostic yield of OI is very high, especially with a large panel 98% and more clear diagnostic statements can be achieved.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1295/

https://www.ncbi.nlm.nih.gov/books/NBK540447/

• Alias: Brittle bone disease
• Alias: Glass bone disease
• Alias: Lobstein disease
• Alias: Osteopsathyrosis
• Allelic: Bone mineral density variability 1 (LRP5)
• Allelic: Bone mineral density variation QTL, osteoporosis (COL1A1)
• Allelic: Deafness, AD 39, with dentinogenesis (DSPP)
• Allelic: Exudative vitreoretinopathy 4 (LRP5)
• Allelic: Hyperostosis, endosteal (LRP5)
• Allelic: IFAP syndrome with/-out BRESHECK syndrome (MBTPS2)
• Allelic: Keratosis follicularis spinulosa decalvans, XL (MBTPS2)
• Allelic: Microcephaly 19, primary, AR (COPB2)
• Allelic: Olmsted syndrome, XL (MBTPS2)
• Allelic: Osteopenia [panelapp] (SUCO)
• Allelic: Osteoporosis (LRP5)
• Allelic: Osteoporosis, early-onset, susceptibility to, AD (WNT1)
• Allelic: Osteoporosis-pseudoglioma syndrome (LRP5)
• Allelic: Osteosclerosis (LRP5)
• Allelic: Polycystic liver disease 4 with/-out kidney cysts (LRP5)
• Allelic: Preterm premature rupture of the membranes, susceptibility to (SERPINH1)
• Allelic: Skeletal dysplasia [HP:0002652, panelapp] (SUCO)
• Allelic: Skeletal dysplasias [panelapp] (NOTCH2)
• Allelic: van Buchem disease, type 2 (LRP5)
• Bruck syndrome 1 (FKBP10)
• Caffey disease (COL1A1)
• Cole-Carpenter syndrome 1 (P4HB)
• Dentin dysplasia, type II (DSPP)
• Dentinogenesis imperfecta, Shields type II (DSPP)
• Dentinogenesis imperfecta, Shields type III (DSPP)
• Ehlers-Danlos syndrome, arthrochalasia type, 1 (COL1A1)
• Ehlers-Danlos syndrome, arthrochalasia type, 2 (COL1A2)
• Ehlers-Danlos syndrome, cardiac valvular type (COL1A2)
• Hyperparathyroidism, transient neonatal (TRPV6)
• Microcephaly 19, primary, AR (COPB2)
• No fracture [panelapp] (DSPP)
• Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (TAPT1)
• Osteogenesis imperfecta + decreased bone density [panelapp] (NOTCH2)
• Osteogenesis imperfecta [MONDO:0019019, panelapp] (SUCO)
• Osteogenesis imperfecta, type I-IV (COL1A1)
• Osteogenesis imperfecta, type II-IV (COL1A2)
• Osteogenesis imperfecta, type V (IFITM5)
• Osteogenesis imperfecta, type VI (SERPINF1)
• Osteogenesis imperfecta, type VII (CRTAP)
• Osteogenesis imperfecta, type VIII (P3H1 syn. LEPRE1)
• Osteogenesis imperfecta, type X (SERPINH1)
• Osteogenesis imperfecta, type XI (FKBP10)
• Osteogenesis imperfecta, type XII (SP7)
• Osteogenesis imperfecta, type XIII (BMP1)
• Osteogenesis imperfecta, type XIV (TMEM38B)
• Osteogenesis imperfecta, type XIX (MBTPS2)
• Osteogenesis imperfecta, type XV (WNT1)
• Osteogenesis imperfecta, type XVI (CREB3L1)
• Osteogenesis imperfecta, type XVII (SPARC)
• Osteogenesis imperfecta, type XVIII (TENT5A syn. FAM46A)
• Osteogenesis imperfecta, type XX (MESD)
• Osteogenesis imperfecta, type XXI (KDELR2)
• Osteootohepatoenteric syndrome (UNC45A)
• Osteopetrosis, AD 1 (LRP5)
• Osteoporosis, childhood- or juvenile-onset, with developmental delay (COPB2)
• Osteoporosis, postmenopausal (COL1A2)
• Recurr. fractures, add. skelet. signs, short-limb dwarfism, bowed legs, scoliosis [panelapp] (NUDT6)