Genetika i kliničke osobitosti sindroma mikrodelecije 22q11.2

master's thesis

• Title (english): Genetics and clinical manifestations of 22q11.2 deletion syndrome
• Author: Morena Surać
• Mentor: Sanda Huljev Frković (mentor)
• Committee member: Nevena Krnić (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Sanda Huljev Frković (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2024-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Sindrom mikrodelecije 22q11.2 (22q11.2DS) najčešći je sindrom mikrodelecije u ljudi, s prevalencijom u općoj populaciji od približno 1 na 4000 živorođene djece. Genetska osnova 22q11.2DS leži u deleciji regije 11.2 na dugom kraku kromosoma 22. Zbog nestabilnosti ove regije i njene sklonosti mutacijama, sindrom obuhvaća heterogenu skupinu bolesti koje se prezentiraju različitim fenotipovima, od kojih je najpoznatiji DiGeorgeov sindrom (DGS).
Delecija regije 22q11.2 uključuje više gena, od kojih su neki ključni za razvoj pojedinih organskih sustava. To rezultira širokim spektrom kliničkih simptoma koji se mogu identificirati u različitim fazama života, kao što su prenatalno razdoblje, novorođenčka dob, djetinjstvo, a ponekad i tek u odrasloj dobi. Ovi simptomi mogu varirati od blagih do teških i često obuhvaćaju kongenitalne srčane greške, dismorfiju lica, hipoplaziju timusa, hipoparatiroidizam i rascjep nepca.
Većina dijagnoza postavi se u ranijoj životnoj dobi, a kongenitalne srčane greške su jedna od temeljnih anomalija pri postavljanju kliničke dijagnoze 22q11.2DS. Cilj ovog diplomskog rada bio je prikazati različite kliničke osobitosti pacijenata s 22q112DS uz prikaz četiri pacijenta koji su se prezentirali atipičnom kliničkom slikom, što je otežalo dijagnostiku i dovelo do kasnijeg postavljanja dijagnoze sindroma.
Naglasak je stavljen na multidisciplinarni i sveobuhvatni pristup pri prepoznavanju i liječenju pacijenata s ovim sindromom, te je istaknuta važnost genetskog testiranja, koje je danas osnovna dijagnostička metoda za potvrdu bolesti. Pravovremeno genetsko testiranje omogućava postavljanje točne dijagnoze, što je ključno za planiranje odgovarajućeg liječenja i praćenja pacijenata, ali ima i važnu ulogu u genetskom savjetovanju obitelji o rizicima za pojavu bolesti u potomstvu i mogućnostima prenatalne dijagnostike.

Abstract (english)

Deletion syndrome 22q11.2 (22q11.2DS) is the most common microdeletion syndrome in humans, with a prevalence in the general population of approximately 1 in 4000 live births. The genetic basis of 22q11.2DS lies in the deletion of region 11.2 on the long arm of chromosome 22. Due to the instability of this region and its susceptibility to mutations, the syndrome comprises a heterogeneous group of diseases with different phenotypes, of which DiGeorge syndrome (DGS) is the best known.
The deletion of the 22q11.2 region affects a large number of genes, some of which are crucial for the development of various organ systems. This leads to a broad spectrum of clinical symptoms that can occur at different stages of life, including prenatal, infancy, childhood and even adulthood. These symptoms can range from mild to severe and often include congenital heart defects, facial anomalies, thymic hypoplasia, hypoparathyroidism and cleft palate.
Most diagnoses are made early in life, with congenital heart defects being one of the fundamental abnormalities in establishing the clinical diagnosis of 22q11.2DS. The aim of this thesis was to present different clinical characteristics of these patients and four patients who presented with a different clinical picture, complicating the diagnosis and leading to a later diagnosis of 22q11.2 deletion syndrome.
The focus was on a multidisciplinary and comprehensive approach to the detection and treatment of patients with this syndrome, emphasizing the importance of genetic testing, which is now the primary diagnostic method for confirming the disease. Timely genetic testing enables accurate diagnosis, which is crucial for planning appropriate treatment and monitoring of patients. However, it also has an important role in genetic counseling of families about the risks of the disease occurring in offspring and the possibilities of prenatal diagnosis.

• Keywords: DiGeorgeov sindrom; genetsko testiranje; kongenitalne anomalije; sindrom mikrodelecije 22q11.2
• Keywords (english): congenital anomalies; deletion syndrome 22q11.2; DiGeorge syndrome; genetic testing
• Language: croatian
• URN:NBN: urn:nbn:hr:105:022954
• 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: 2024-06-24 16:26:32