Title Ishodi novorođenčadi s prenatalno dijagnosticiranim tumorima srca Title (english) Outcomes of infants with prenatally diagnosed heart tumors Author Ana Ćorić Mentor Ruža Grizelj (mentor)Committee member Daniel Dilber (predsjednik povjerenstva)Committee member Marija Jelušić (član povjerenstva)Committee member Ruža Grizelj (član povjerenstva)Granter University of Zagreb Defense date and country 2020-07-17, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Rabdomiomi srca (RS), iako rijetki, najčešći su fetalni tumori srca. Smatraju se jednom od najranijih manifestacija tuberozne skleroze (TSC). TSC se otkriva u 75-80% bolesnika s multiplim i u oko 30% bolesnika sa solitarnim RS. Provedeno je retrospektivno istraživanje ishoda novorođenčadi kojima je u periodu od 2009. do 2019. godine u referalnom tercijarnom centru prenatalno otkriven tumor(i) srca. Identificirali smo 14 bolesnika. Prosječni period praćenja bio je 4 godine (raspon: 4 mjeseci-9 god.). Dva fetusa su bili blizanci (diamnijski-dikorionski), oboje s RS i pozitivnom obiteljskom anamnezom za TSC. U drugom dikorinskom paru blizanaca, jedan nije bio zahvaćen RS. Prosječna gestacijska dob (GD) bila je 29 tjedana (raspon: 21-35 tj.). Jedanaest fetusa imalo je multiple, a tri solitarne tumore. RS su se nalazili podjednako u desnom i lijevom ventrikulu s blagom dominacijom lijevog ventrikula. Atriji su bili zahvaćeni u dva slučaja. Veličina tumora varirala je od par mm do veličine 20x20 mm. Dva fetusa razvila su hemodinamski značajnu opstrukciju izlaznog trakta lijevog ventrikula (LVOT), a u četvero su uočene aritmije (SVES, VES, WPW sindrom i AV blok). Nije zabilježen niti jedan fetalni hidrops niti fetalna smrt. U 11 bolesnika (79%) TSC je potvrđena klinički ili genskom analizom. Nakon rođenja, u većine bolesnika RS nisu mijenjali veličinu (14%, n=2), ili je s vremenom nastupila njihova spontana regresija (57%, n=8). U 71% bolesnika veličina tumora bila je < 20 mm. U četvero djece (29%) RS su potpuno nestali. U niti jednom slučaju, nije uočen rast ili porast broja tumora. U petero djece (36%) nakon poroda dijagnosticirani su poremećaji provođenja koji su dobro reagirali na antiaritmičku terapiju. Dvoje djece je imalo hemodinamski značajnu LVOT opstrukciju. Cerebralne manifestacije bolesti (tuberi i/ili noduli) uočene su analizom magnetske rezonancije (MR) u 9 bolesnika (3 prenatalno). Subependimalni gigantocelularni astrocitom (SEGA) dijagnosticiran je u 3 slučaja, u dvoje je započeta terapija mTOR inhibitorima, dok je u trećeg bolesnika zbog rasta SEGA i opstruktivnog hidrocefalusa postavljena ventrikulo-peritonealna drenaža. Šestero bolesnika (55%) s dijagnozom TSC, boluje od epilepsije i zaostaje u psihomotornom razvoju. Iako su iz kardiovaskularne perspektive RS benigni tumori s tendencijom spontane regresije, njihova značajna povezanost s TSC zahtijeva postavljanje rane prenatalne dijagnoze i obiteljsko savjetovanje. Recentna istraživanja predlažu rano započinjanje terapijom mTOR inhibitorima koji su se pokazali obećavajućima u prevenciji simptoma TSC.
Abstract (english) Although rare, cardiac rhabdomyomas (CRs) are the most common fetal cardiac tumors. They may be the earliest manifestation of tuberous sclerosis complex (TSC). TSC is diagnosed in 75-80% cases of multiple fetal CRs and in 30% of single cases. We retrospectively reviewed the clinical outcome of fetal CR cases. All cases of prenatally diagnosed rhabdomyoma in a single tertiary centre from 2009 to 2019 were ascertained from medical records. We identified 14 fetuses with prenatally diagnosed CRs. Mean period of follow-up was 4 years (range 4m-9y). Two fetuses were twins (BC/BA), both affected by CR with family history of TSC, and one fetus of the dichorionic pair was not affected by rhabdomyoma. The mean GA at diagnosis was 29 weeks (range 21-35). There were eleven fetuses with multiple, and three with a solitary tumor. The right and left ventricle were equally affected with a slight predominance of the left ventricle. The cardiac atrium was affected in two cases. The size ranged from small tumors of several mm in diameter up to dimensions of 20x20 mm. Two of fetuses were affected by hemodynamically relevant cardiac obstruction (LVOT), and in four arrhythmias (SVES, VES, WPW syndrome, and AV block) were observed. No hydrops fetalis or fetal perinatal demise were observed. In 11 (79%) TSC was confirmed clinically or by mutational analysis. After birth, most rhabdomyomas demonstrated a stable (14%, n=2) or spontaneous regressive growth pattern (57%, n=8). Seventy one precent of tumors were < 20 mm. In four children (29%) tumors entirely disappeared. No progression of tumor size or number was observed. After birth in five (36%) children the conduction abnormalities were confirmed by ECG and responded well to the anti-arrhythmic medication and two children were affected by LVOT obstruction. Cerebral manifestations (tubers and/or nodules) were detected by brain MRI in 9 patients (3 prenatally). Subependymal giant cell astrocytoma was diagnosed in 3 cases, 2 received treatment with mTOR inhibitor, and one child underwent VP shunt due to enlarging SEGA causing obstructive hydrocephalus. Six (55%) of the children with TSC suffered from epilepsy and psychomotoric development delay. Although CRs are benign from the cardiovascular standpoint, and have a natural history of spontaneous regression, their close association with TSC prompt for early prenatal diagnosis and family counselling regarding the dismal long-term prognosis. Recent literature suggests that early therapy with mTOR inhibitors may prevent the development of TS manifestations.
Keywords
rabdomiomi srca
tuberozna skleroza
mTOR inhibitori
Keywords (english)
cardiac rhabdomyomas
tuberous sclerosis
mTOR inhibitors
Language croatian URN:NBN urn:nbn:hr:105:990945 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2021-05-10 11:25:52
