Multiple hereditarne egzostoze

master's thesis

• Title (english): Hereditary multiple exostoses
• Author: Vilim Molnar
• Mentor: Tomislav Đapić (mentor)
• Committee member: Domagoj Delimar (predsjednik povjerenstva)
• Committee member: Tomislav Smoljanović (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

Multiple hereditarne egzostoze su autosomno dominantni nasljedni poremećaj koji se očituje stvaranjem benignih tumora kosti u djece, osteohondroma. Iako je bolest rijetka, a tumori benigni, ona može izazvati niz komplikacija već u dječjoj dobi. Bolest je najčešće uzrokovana mutacijama EXT1 i EXT2 gena koje dovode do pogreške u proliferaciji i maturaciji hondrocita što rezultira abnormalnim koštanim rastom i stvaranjem egzostoza. Gotovo svaka kost ili zglob mogu biti zahvaćeni egzostozom, osim kostiju lica, jer one rastu intramembranoznom osifikacijom, drugačijim procesom rasta nego u dugim kostima. Osteohondromi svojim rastom interferiraju s normalnim rastom dovodeći do deformacija skeleta, pritišću okolne strukture, uzrokuju bol, smanjuju opseg pokreta bolesnika, ali i stvaraju brojne specifičnije komplikacije bolesti, među kojima je najteža maligna degeneracija tumora. Težina kliničke slike ovisi o mnogim faktorima, a ponajviše o mutiranom genu te spolu. Brojne studije pokazale kako je teži fenotip povezan s mutacijama EXT1 gena i muškim spolom. Veći broj tumora, manja tjelesna visina, veći skeletni deformiteti, kraći udovi i veća uključenost ravnih kosti poput zdjelice i lopatice, a tako i veći broj maligno degeneriranih tumora zabilježeni su u pacijenata mutacijom EXT1. Bolest ne samo da uzrokuje fizičke simptome i bol, već ima i negativan utjecaj na socijalno funkcioniranje bolesnika i njegovu kvalitetu života. Za određene karakteristične deformitete, kirurško liječenje može prevenirati progresiju deformiteta ili ga čak i ispraviti. Ono se provodi ekscizijom lezija, rekonstruktivnom kirurgijom te kirurgijom kontrole rasta.

Abstract (english)

Hereditary multiple exostoses is an autosomal dominant inherited genetic condition characterized by the formation of benign bone tumors in children, osteochondromas. Even though the incidence of MHE is low, the disease can result in numerous complications in the early age. The disorder is caused by mutations in the EXT gene family, resulting in an error in proliferation and maturation of chondrocytes, leading to abnormal bone growth and exostoses formation. Mainly all the bones in the human body can be affected by an exostosis, except facial bones because they grow by intramembranous ossification. Osteochondromas interfere with normal bone growth leading to skeletal deformations, compress underlying tissue, cause pain, decrease range of motion and result in many different and specific complications, of which the most dangerous is a malignant transformation of the tumor. The phenotype depends on numerous factors, but mostly on male gender and mutated gene. Several studies have suggested the correlation between a more severe phenotype and EXT1 mutation. A larger number of tumors, lower body height, more severe deformities and a larger number of flat bone lesions such as lesions of pelvis and scapula, but also increased the incidence of malignant change were associated with EXT1 mutation. MHE doesn't only cause pain and physical symptoms, but also on social wellbeing and quality of life. For certain deformities, surgical therapy can prevent progression or even repair the deformity. The types of surgical treatment are lesion excision, reconstructive surgery and growth control surgery.

• Keywords: osteohondrom; djeca; deformacije; maligna alteracija; kirurško liječenje
• Keywords (english): osteochondroma; children; deformities; malignant transformation; surgical treatment
• Language: croatian
• URN:NBN: urn:nbn:hr:105:550520
• 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: 2020-02-11 09:02:34