Sestre Milosrdnice University hospital and Institute of Clinical Medical Research
Abstract
Osteogenesis imperfecta is a genetically and clinically heterogeneous disorder of bone and connective tissue characterized by osteoporosis, fragile bones, hyperextensible joints, dentinogenesis imperfecta, bluish coloration of the sclerae, and adult-onset hearing loss. Medical history, careful physical examination, radiographic features of fractures, and biochemical analysis of skin collagen are the four cornerstones of accurate diagnosis. As osteogenesis imperfecta affects the whole skeleton, radiologic diagnostic features could be seen on any bone at any age of the patient. A radiology specialist should be aware of subtle changes seen on radiographs of axial skeleton (i.e. skull, spine and pelvic bones) and appendicular skeleton (i.e. long and short bones of extremities) as well as of specific osteogenesis features (i.e. “popcorn” calcifications) and difficult differential diagnosis (i.e. hypertrophic callus formation versus osteosarcoma; child abuse fractures versus true osteogenesis imperfecta). About 300 different mutations have been identified within COL1A1 and COL1A2 genes that encode the chains of type I collagen. More than 90% of these are heterozygous single base pair mutations unique to the affected individuals within families. Depending on the location of the mutation within the collagen gene, these produce a variety of clinical pictures which range from mild (OI type 1), lethal (OI type 2) to severely deforming (OI type 3) and mildly deforming (OI type 4). Each of the four types has a common radiologic appearance that helps in establishing the diagnosis. However, recent findings have confirmed that new genes other than type I collagen could be responsible for three new types of OI (OI type 5; OI type 6 and rhizomelic OI). Here we describe the complexity of the phenotype-genotype correlation in OI, and the recently proposed new classification.Osteogenesis imperfecta (OI) je genetski i klinički heterogena bolest kosti i vezivnoga tkiva s odrednicama: osteoporoza; lomljivost kostiju; labavost zglobova, dentinogenesis imperfecta; plavičaste bjeloočnice i nagluhost u odrasloj dobi. Ključ točne dijagnoze su četiri bitna postupka: precizna anamneza; pažljiv fizikalni pregled; uočavanje radioloških značajka prijeloma i promjena kostiju i biokemijska analiza kolagena kože. Uobičajena je podjela na četiri tipa OI: od blagog (tip 1), letalnog (tip 2) do teško deformirajućeg (tip 3) i umjereno deformirajućeg oblika (tip 4). Svaki od četiri tipa ima zasebne radiološke značajke koje pomažu kod postavljanja točne dijagnoze i klasificiranja. Dijagnostičko-radiološki znaci postoje na cijelom mišićno koštanom sustavu od novorođenačke do kasne životne dobi. Za radiologa je važno prepoznati brojne sićušne i specifične promjene na rendgenogramima aksijalnog (lubanja, kralješnica, zdjelica) i apendikularnog (kosti udova) skeleta. Znaci korisni u diferenciranju osteosarkoma prema stvaranju hipertrofičnog koštanog kalusa kod OI i drugi posebni znaci bolesti, primjerice metafizne “popcorn” kalcifikacije, prepoznaju se dobrom radiološkom obradom. Dosad je otkriveno oko 300 različitih mutacija na COL1A1 i COL1A2 genima odgovornima za oblikovanje lanaca kolagena tip I. Klinička slika OI razlikuje se prema mjestu mutacije na genu za kolagen. Nedavni nalazi su potvrdili da i drugi geni, uz kolagen tip 1, mogu biti odgovorni za nastanak tri nova tipa OI: tip 5; tip 6 i rizomelični tip OI. Nadalje, u tekstu je opisana složenost fenotipske i genotipske korelacije, kao i nedavno predložena nova klasifikacija OI
