Analiza govorno-jezičkog, socio-emocionalnog i kognitivnog razvoja bolesnika sa heterozigotnom mikrodelecijom regiona q11.2 na hromozomu 22

Sažetak: Sindrom delecije 22q11.2 (22q11.2DS) karakteriše prisustvo heterozigotne mikrodelecije regiona q11.2 na hromozomu 22. Pokazano je da deca sa 22q11.2DS često kasne na polju govorno-jezičkog, socio-emocionalnog i kognitivnog razvoja. Kako u literaturi nema podataka o ovim sposobnostima kod bolesnika sa 22q11.2DS govornika južno-slovenskih jezika, u okviru ove doktorske disertacije analizirane su govorno-jezičke, kognitivne i socio-emocionalne sposobnosti bolesnika sa 22q11.2DS izvornih govornika srpskog jezika. Dijagnoza 22q11.2DS postavljena je na osnovu prisustva najmanje dve od pet najčešćih fenotipskih karakteristika 22q11.2DS (urođene srčane malformacije konotrunkalnog tipa (KSM), facijalna dismorfija, aplazija/hipoplazija timusa, rascep nepca, hipokalcemije). Za detekciju mikrodelecije 22q11.2 primenjene su fluorescentna in situ hibridizacija (FISH) i metoda višestrukog umnožavanja proba koje je zavisno od ligacije (MLPA). Na osnovu rezultata FISH i/ili MLPA metoda, bolesnici sa kliničkom dijagnozom 22q11.2DS svrstani su u eksperimentalne grupe E1 (kod kojih je detektovana mikrodelecija 22q11.2) i E2 (kod kojih mikrodelecija 22q11.2 nije detektovana). Familijarna forma 22q11.2DS utvrđena je kod četiri porodice. Kako su kod svih bolesnika grupa E1 i E2 detektovane KSM i kako one mogu da utiču na razvoj govorno-jezičkih, kognitivnih i socio-emocionalnih sposobnosti istraživanjem su bila obuhvaćena i bolesnici sa nesindromskim KSM kod kojih mikrodelecija 22q11.2 nije detektovana FISH metodom (grupa E3). Govorno-jezičke, kognitivne i socioemocionalne sposobnosti bolesnika grupa E1, E2 i E3 su poređene sa ovim sposobnostima vršnjaka urednog govorno-jezičkog, socio-emocionalnog i kognitivnog razvoja, dobrog zdravstvenog stanja bez prisutnih hroničnih bolesti (grupa K). Rezultati istraživanja su pokazali da bolesnici grupe E1 imaju lošije govorno-jezičke sposobnosti u poređenju sa bolesnicima grupa E2 i E3 i ispitanicima grupe K. Niži nivo psihofizioloških sposobnosti detektovan je kod bolesnika grupe E1 u poređenju sa bolesnicima grupa E2 i E3 i ispitanicima grupe K... 22q11.2 deletion syndrome (22q11.2DS) is caused by a heterozygous microdeletion of region q11.2 of chromosome 22. It has been shown that speech and language, cognitive and socio-emotional impairments are very common in children with 22q11.2DS. To the best of our knowledge, there are no published data about these abilities in children with 22q11.2DS, native speakers of South-Slavic languages. Therefore, the main goal of this Doctoral Dissertation is to analyze speech and language, cognitive and socio-emotional abilities of children with 22q11.2DS, monolingual native speakers of the Serbian language. Enrollment of patients was based on the presence of at least two out of the five major characteristics of 22q11.2DS (congenital heart malformations (CHM), facial dysmorphism, thymic aplasia/hypoplasia, palatal clefts and hypocalcemia). Fluorescent in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) have been applied in order to detect 22q11.2 microdeletion. Based on FISH/MLPA results, patients with phenotypic features of 22q11.2DS were divided into experimental groups E1 (with 22q11.2 microdeletion) and E2 (without the 22q11.2 microdeletion). A familial form of 22q11.2DS was detected in four families. Patients with non-syndromic CHM (group E3) were included in the study since literature data implies that these children may exhibit a speech and language, cognitive and socioemotional impairments. Applying FISH, 22q11.2 microdeletion was not detected in these patients. Speech-language, cognitive and socio-emotional abilities of patients from the groups E1, E2 and E3 were compared to their age peers with proper speechlanguage, cognitive and socio-emotional development, and good general health condition without chronic diseases (group K). Obtained results revealed that patients from group E1 have less developed speech and language skills and psychophysiological abilities compared to patients from group E2 and E3 and children from group K. Also, cognitive abilities of 38.9% of patients from group E1, 18.8% of patients from group E2 and 25% of patients from group E3 did not reach levels expected for their calendar age...