Progresivna osificirajuća fibrodisplazija

master's thesis

• Title (english): Progressive ossifying fibrodysplasia
• Author: Neva Gatin
• Mentor: Tomislav Đapić (mentor)
• Committee member: Mislav Jelić (predsjednik povjerenstva)
• Committee member: Ivo Barić (član povjerenstva)
• Committee member: Tomislav Đapić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Orthopedics); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Orthopedics

Abstract

Progresivna osificirajuća fibrodisplazija (FOP), poznata kao Munchmeyerova bolest, rijetka je i teško onesposobljavajuća bolest vezivnog tkiva karakterizirana kongenitalnim malformacijama nožnih palčeva i progresivnom heterotopičnom osifikacijom koja dovodi do teških deformiteta. FOP je rijetka bolest, javlja se kod 1 na 2.000.000 stanovnika, bez ikakve rasne, spolne i geografske predilekcije. Mutacija u genu ACVR1 dovodi do akumulacije i pretjerane osteoinduktivne aktivnosti ACVR1/ALK2 receptora u stanicama FOP-a. Mutacija se nasljeđuje autosomno dominantno, iako je većina slučajeva sporadična zbog niskog reprodukcijskog potencijala oboljelih od FOP-a. Upalni procesi također sudjeluju u stvaranju lezija FOP-a, čiji razvitak počinje bolnom oteklinom te progredira do formiranja heterotopne kosti. Bolest je neizbježno progradirajuća, nastaje sekundarni skelet koji onemogućava pokretljivost zahvaćenih dijelova tijela te dovodi do teških komplikacija opasnih po život. Djeca oboljela od FOP-a nakon rođenja djeluju zdravo, izuzev malformacije nožnih palčeva, koji su skraćeni i u valgus položaju. Ovaj nalaz trebao bi biti dovoljan da probudi sumnju u svakom kliničaru, odnosno za postavljanje kliničke dijagnoze. Unatoč tome u 90% pacijenata pogrešno se postavlja dijagnoza te se podvrgavaju zahvatima i dijagnostičkim metodama koje pogoduju progradiranju bolesti. Od iznimne je važnosti pravodobno postaviti dijagnozu, kako bi se izbjegli precipitirajući faktori za pojavljivanje lezija, kao što su trauma mekog tkiva, intramuskularne injekcije, mandibularni blokovi i kirurški zahvati.

Abstract (english)

Fibrodysplasia ossificans progressiva, also known as Munchmeyer's disease, is a rare and severely disabling connective tissue disorder, characterized by congenital malformations of the big toe and progressive heterotopic ossification which leads to debilitating deformities. FOP affects 1 out of 2 million people, without any racial, sex or geographical predilection. A recurrent mutation in activin receptor IA/activin-like kinase-2 (ACVR1/ALK2) exists in all sporadic and familial cases of classic FOP. The mutation is transmitted as a dominant trait, although most cases are sporadic, due to low reproductive fitness. Inflammation is a key component in the formation of FOP lesions, whose development begins with a painful swelling, which develops over time until heterotopic bone has formed at the site. The disease is inevitably progressive, a second skeleton develops over time, disabling the patients’ mobility and confining them in a wheelchair by the third decade of life and often succumbing to pulmonary complications. Children affected by FOP appear healthy at birth, with the exception of malformations of the big toes. Despite this finding being sufficient for a clinical diagnosis, 90% of patients are misdiagnosed and undergo procedures that precipitate progression of the disease. It is crucial to diagnose the patients correctly so precautionary measures to avoid clinical deterioration can be implemented in the patients’ care. These measures are avoiding soft tissue trauma, intramuscular injections, mandibular block and surgical procedures.

• Keywords: progresivna osificirajuća fibrodisplazija; heterotopna osifikacija; mutacija ACVR1
• Keywords (english): fibrodysplasia ossificans progressiva; heterotopic ossification; ACVR1 mutatio
• Language: croatian
• URN:NBN: urn:nbn:hr:105:278407
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-06-10 10:48:27