Clinical aspects of 22q11.2 microdeletion syndrome / A 22q11.2-microdeletiós szindróma klinikai jellemzoi.

Összefoglaló. Bevezetés: A sokszínu tünetspektrummal jellemezheto DiGeorge-szindróma leggyakoribb oka a 22q11.2-microdeletio; incidenciája 1/4000-6000. Célkituzés: A DiGeorge-szindrómára gyanús hazai betegcsoport 22q11.2-microdeletióval társult tüneteinek/panaszainak részletes feltérképezése, a betegség incidenciájának becslése és egy magyarországi 22q11.2-microdeletiós szindróma regiszter létrehozása. Módszer: 2005 és 2019 között a Semmelweis Egyetem II. Gyermekgyógyászati Klinikájára DiGeorge-szindróma gyanújával beutalt és a Veleszületett Rendellenességek Országos Nyilvántartása által regisztrált DiGeorge-szindrómás betegek adatait dolgoztuk fel. A fenotípusjegyeket a Humán Fenotípus Ontológia kódrendszer alapján határoztuk meg. Eredmények: A vizsgálatba 114, igazolt DiGeorge-szindrómás és 113, FISH-vizsgálattal microdeletiót nem hordozó, de klinikailag a DiGeorge-szindróma tüneteit mutató beteget vontunk be. A diagnózis felállításakor a betegek átlagéletkora 5,88 (± 9,66 SD) év volt, eddig a betegek 54,9%-a legalább egy szívmutéten átesett. A betegek leggyakoribb tünetei a kamrai sövényhiány, a mélyen ülo fülek, a gótikus szájpad, a motoros fejlodési elmaradás és a visszatéro fertozések voltak. Megbeszélés: A DiGeorge-szindróma becsült incidenciája hazánkban 1/12 500, közöttük magas a többszörösen veszélyeztetett újszülöttek és a mutéti korrekcióra szorulók aránya. A diagnózis hazánkban 2-3 évvel korábban történik a nemzetközi átlaghoz viszonyítva. Következtetés: A létrehozott regiszterünk alapján Magyarországon a kórkép aluldiagnosztizált. Minden conotruncalis szívfejlodési rendellenesség vagy jelentos kamrai sövényhiány esetén citogenetikai vizsgálat javasolt a DiGeorge-szindróma felmerülo gyanúja miatt. Negatív lelet esetén az atípusos töréspontú microdeletiók azonosítására komparatív genomiális hibridizáció vagy multiplex ligatiofüggo próbaamplifikációs vizsgálat javasolt. A betegek számára multidiszciplináris ellátás szükséges, III-as progresszivitási szintu újszülött intenzív részlegen, gyermekkardiológus és klinikai genetikus részvételével. Orv Hetil. 2022; 163(1): 21-30. INTRODUCTION: The 22q11.2 microdeletion syndrome is the most common cause of DiGeorge syndrome, showing a wide phenotypic spectrum and has an estimated incidence of 1/4000-6000 livebirths. OBJECTIVE: Detailed characterization of the clinical signs/symptoms associated with 22q11.2 deletion, estimation of the national incidence via establishing a Hungarian register. METHOD: Retrospective data between 2005 and 2019 from the 2nd Department of Paediatrics, Semmelweis University and from national database of congenital anomalies were obtained. Phenotypic abnormalities were described using the Human Phenotype Ontology nomenclature. RESULTS: A cohort of 114 DiGeorge patients and 113 patients negative for FISH testing were included. The mean age of patients at diagnosis was 5.88 (± 9.66 SD) years and 54.9% of patients had at least one heart surgery until diagnosis. The main identified symptoms were ventricular septal defect, low-set ears, recurrent infections, high narrow palate and motor development delay. DISCUSSION: The estimated incidence of DiGeorge syndrome in Hungary is 1/12 500 births, the frequency of infants at high risk and in need for surgery is high. Diagnosis is established 2-3 years earlier as compared to the international average. CONCLUSION: Based on the established Hungarian register, the incidence is lower compared to international data. In the case of conotruncal heart anomaly and ventricular septal defects, cytogenetic testing is recommended for the increased probability of DiGeorge syndrome. For second-tier testing, comparative genome hybridization or multiplex ligation-dependent probe amplification are recommended to identify atypical microdeletions. Newborns with DiGeorge syndrome require special care in perinatal intensive centers including pediatric cardiology and genetic counseling. Orv Hetil. 2022; 163(1): 21-30.

[Multivalve redo surgery in adult patient with complex pulmonary artesia]. / Több-billentyus redomutét felnott betegen komplex pulmonalis atresiában.

30-year-old adult with complex pulmonary atresia (previous surgical procedures: in infancy: exploration, at age of 10: ventricular septal defect closing, unifocalization, homograft implantation between right ventricular outflow tract and pulmonary artery) has biventricular dysfunction because of aortic valve regurgitation, ascending aortic aneurysm, and homograft insufficienty. Multivalve surgery: aortic valve plasty, pulmonary homograft changes for homograft and ascending aortic reconstruction by graft were carried out successfully. In Hungary this was the first case of this type of surgery. Management of special problems (follow-up, correct diagnostics (echocardiography, MR, CT), indication and necessity of reoperation, optimal age) in adult patients with complex congenital heart defects produces excellent early and late surgical results. Orv. Hetil., 2017, 158(14), 546-549.

[Role of the Ross-procedure in the management of congenital heart defects]. / A Ross-mutét helye a veleszületett szívhibák sebészi kezelésében.

INTRODUCTION: The surgical strategy to manage multilevel left ventricular outflow tract diseases is changing constantly, however, the Ross-procedure has remained a standard method for 45 years. AIM: The aim of the study was to analyze early and mid-term results of Ross-procedure in congenital heart defects (single surgeon's results). METHODS: From 2001 until 2011 a total of 63 patients (age, 28 days-21 years; mean: 10 years, weight 3.4-96 kg; mean, 8.8 kg) underwent Ross (n = 40), Ross-Konno (n = 17) or Ross-Konno-mitral (n = 6) procedures. Indication for Ross procedure was aortic regurgitation in 15 patients (associated with ventricular septum defect in 8 patients) and a predominant aortic stenosis in 25 patients. 17 patients with severe left ventricular outflow tract obstruction underwent Ross-Konno procedure. 6 patients with concomitant mitral valve disease (Shone syndrome, 3 patients; complete atrioventricular septal defect, 3 patients) were reconstructed by Ross-Konno-mitral valve procedure. RESULTS: Among Ross patients there were one early (cerebral complication) and one late death (homograft endocarditis) with a mean follow-up time of 7.4±1.8 years. Because of an early autograft endocarditis a 3-year-old boy underwent homograft implantation and was treated successfully with Bentall-procedure 9 years later. One patient with autograft regurgitation is waiting for reoperation. Among Ross-Konno patients there was no early or late death, and none of the patients underwent reoperation. In Ross-Konno-mitral patients there was one early death (28-day-old boy) and during a mean follow-up time of 2.5±1 years, and no reintervention or reoperation was needed in 5 patients. CONCLUSIONS: The results indicate a good outcome of Ross-, Ross-Konno-, Ross-Konno-mitral procedures in patients with congenital heart defects when surgery is performed by a highly experienced heart surgeon. In newborns, infants and small children Ross- and Ross-Konno procedures are the only methods for managing left ventricular outflow tract diseases. Concomitant severe mitral disease adds a high level of technical complexity to the Ross-Konno/mitral procedure, but it should be balanced against alternative strategies (eg. single ventricle palliation or transplantation).

[Right ventricular outflow tract reconstruction in adolescents and adults after previous repair of congenital heart defects]. / A jobbkamra-kifolyási pálya rekonstrukciója elozoleg korrigált veleszületett szívhibák esetén fiatal- és felnottkorban.

UNLABELLED: Due to successful surgical treatment of congenital heart defects in infants and children, the number of patients who reach the adolescent/adult age is continuously increasing. AIMS: The authors sought to identify the short- and medium-term outcomes of reconstruction of right ventricular outflow tract in adolescents and adults who underwent surgical intervention for congenital heart defect in infancy or early childhood. METHODS: Between 2001 and 2012, 48 patients (age: 15-39, mean 21 years) (30 tetralogy of Fallot, 11 pulmonary atresia + ventricular septal defect, 6 transposition of great arteries + ventricular septal defect + left ventricular outflow tract obstruction, and 1 truncus arteriosus) had repeat operation because of right ventricular dysfunction. All patients previously underwent right ventricular outflow tract procedures in early childhood. RESULTS: In 31 patients, the small homograft, and in 9 patients the transannular-paths were replaced for "adult-size" homograft. Bioprosthetic pulmonary valve replacement was performed in pulmonary (6 patients) and homograft annuli (2 patients). In 14 patients, resection of the right ventricular outflow tract aneurism was also necessary to be performed. There was no early and mid-time (10 years) mortality. In 97.5% of patients with homograft-re-implantation, there was no need for repeat intervention for 5 years. CONCLUSIONS: The right ventricular outflow tract restoration in adolescents and adults is an effective procedure. The reconstruction should be performed in early adolescent period to prevent right ventricular dysfunction. The authors prefer using bioprosthetic pulmonary valve replacement in patients with adult-size pulmonary or homograft annulus.

[Redo procedures for correction of aortic valve diseases in infants and children. The Bentall-Konno procedure]. / Csecsemô- és gyermekkori REDO mûtéteket igénylô aortabillentyû-betegség. Az elsô magyarországi Bentall-Konno-mûtét gyermekkorban.

On an infant with critical valvular aortic stenosis balloon-valvoplasty, and 3 years later because of the aortic valve regurgitation Ross operation was performed. In the early postoperative period an aortic-root abscess occurred due to an infective endocarditis; the aortic root was corrected by homograft implantation. Due to a relatively small, calcified aortic valve, with aortic valve regurgitation grade III at the age of 12 years, a Bentall-Konno procedure was performed successfully. This is the first case when this complex surgical procedure was performed successfully on a child in Hungary.

[Management of Fabry disease]. / Fabry-betegség - terápiás útmutató

Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive and the first symptoms usually present in childhood. Consequences of the disease are disability and premature death. The disease in females could be as severe as in males although women may be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline has been summarized by a Hungarian multi-disciplinary working group consisting of physicians who are involved in diagnosis and care of Fabry patients. Previous clinical studies, published articles, and recently established international treatment guidelines were reviewed by the group.

[Fabry disease--diagnostic guideline]. / Fabry-betegség. Diagnosztikai útmutató.

Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive, first symptoms usually present in childhood. Consequencies of the diseases are disability and premature death. The disease in females could be as severe as in males although women may also be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline was established by a Hungarian multi-disciplinary working group, consisting of physicians who are involved in health care of Fabry patients. Previous clinical studies, published materials, and recently established international treatment guidelines were reviewed by the group.

[Surgical management of anomalous origin of the left coronary artery from the main pulmonary artery with Takeuchi procedure]. / Takeuchi mutét, egy ritka szívmutét elso sikeres hazai alkalmazása.

Anomalous origin of the left coronary artery from the main pulmonary artery is a rare form of congenital heart disease. It carries a very poor prognosis with a mortality rate of more than 85% in the first year of life due to severe left ventricular failure. Surgical repair results in progressive improvement of left ventricular function even in patients with a severely damaged myocardium. The current surgical management is to reimplant the anomalous origin of the left coronary artery from the pulmonary artery to the aorta. Historically, ligation of the anomalous origin and a subclavian artery-left coronary artery bypass were carried out. A 20-month-old boy underwent a Takeuchi procedure (a fenestration between the aorta and the main pulmonary artery, an intrapulmonary tunnel between the orifice of anomalous left coronary artery and fenestration, and a pulmonary artery reconstruction), because the reimplantation of the anomalous coronary artery was technically impossible. The success of this procedure was proven by good early result.

[Quantification of right and left ventricular function with magnetic resonance imaging after Senning operation for complete transposition of the great arteries]. / Mágneses rezonancia vizsgálat a jobb es bal kamra funkciójának megítélésére nagyér-transzpozíciós gyermekek Senning-mutétje után.

INTRODUCTION: The different non-invasive examinations do not result in unambigous results about the long-term determination of right ventricular function providing systemic circulation in children with transposition of the great arteries operated with Senning procedure. AIM: The goal of study was to determine the application of MRI for the observation of right and left ventricular morphology and function, for the recognition of the progression of the disease, and for the necessity of reoperation. METHODS: The authors have observed the morphology and function of the right and left ventricule by ECG triggered short axis MR pictures. For the analysis of MR pictures MASS 5.0 software was used. Authors have determined the end systolic and end diastolic volume, the ejection fraction, the mass, and the stroke volume of the right ventricule, the end systolic and end diastolic volume, ejection fraction, the mass, and the stroke volume of the left ventricle, and the shunt volume. The values of these data corrected to body mass have been calculated. PATIENTS: 176 Senning operations took place between 1980 and 1996. MRI exploration at 21 of the 118 analyzed patients were carried out. RESULTS: The right ventricular ejection fraction value at Senning operated patients is significantly different (49 +/- 9% vs. 70 +/- 4%) from those of healthy children (P < 0.01). Right ventricular stroke volume/m2 and right ventricular end systolic volume/m2 were significantly different compared to normal (43 +/- 10 ml/m2 vs. 48 +/- 7 ml/mn and 46 +/- 16 ml/m2 vs. 21 +/- 5 ml/m2, p < 0.05). Authors found also significant differences in left ventricular ejection fraction in Senning patients as compared to normal (60 +/- 9% vs. 70 +/- 6%, p < 0.01). CONCLUSION: MRI, which is a reliable method of objective determination of right ventricular function, became an available method in Hungary. According to the results, authors might presume that the development of right ventricular dysfunction is expected even among Senning operated children without clinical symptoms, so more frequent control is required. The pathological left ventricular parameters may be explained by ventricular interactions. Authors find MRI an important part of the complex follow-up protocol of Senning operations. MRI data extended by results of other non-invasive explorations are appropriate for the follow-up of right ventricular dysfunction.

[Prognosis for the fetus with congenital heart defects in the era of modern diagnostics and therapeutics]. / Szívfejlódési rendellenességben szenvedó magzatok életkilátásai a modern diagnosztika és terápia feltételei között.

BACKGROUND: Prenatal detection of structural heart diseases and rhythm disturbance has become possible using echocardiography. Authors have already documented the high diagnostic accuracy of intrauterin diagnosis of heart diseases in our country as well. AIM OF THIS STUDY: To examine the prognosis of fetal cardiac diseases diagnosed by echocardiography in the institute between 1985-2001. METHODS: The prognosis of 223 (6.3%) cardiac anomalies found in 3468 fetal echocardiograms was assessed by postnatal echo/surgery/or autopsy. RESULTS: The authors detected cardiac anomalies in 153, rhythm disturbance in 70 fetuses. They could follow (mean 4.2 yrs) the 83% of patients by postnatal echo/surgery or autopsy. They lost 46 pts (36%) by elective termination, intrauterine death, or during the postnatal period. 83% of these pts had hypoplastic left heart syndrome, fibroeleastosis, or aortic stenosis. Right heart anomalies (tetralogy of Fallot, critical pulmonary stenosis etc.) showed good prognosis with early surgical or catheter intervention. Isolated fetal supraventricular tachycardias can be successfully treated prenatally, and fetal complete heart block by emergency postnatal permanent pacemaker implantation. CONCLUSIONS: Fetal echocardiography must be considered in our country also such a method which can influence the natural history of fetal heart diseases. The result of infant cardiac surgery also dramatically improved, so we think this knowledge is very important during the counselling.

Aortic root abscess with aortico-mitral discontinuity after a ross operation in a child: reconstruction with an oversized homograft.

A case of early neo-aortic root abscess following a Ross operation in a 3(1/2)-year-old child is described. The infection destroyed neo-aortic wall with two of the semilunar leaflets detached, and the abscess cavity extended across the intervalvular fibrous body into the left atrium and onto the native mitral valve creating partial "aortico-mitral discontinuity." Reconstruction was successful with an oversized cryopreserved homograft.

[New strategies in surgical management of coarctation of the aorta 1975-2001]. / Szemléletváltozás a coarctatio aortae sebészi kezelésében 1975-2001.

AIM: This article presents the early and late surgical results of 401 newborns and infants among the 569 children with coarctation of aorta who were operated on between 1975-2001. RESULTS: The early results were dependent on the anatomy of the aortic arch, the age and weight of babies and the types of the associated heart defects. The mortality rate was reduced from 15% (isolated coarctation 7.3%, complex coarctation 34%) to 3.0% (isolated 1.9%, complex 4.9%). 77.3% of 320 infants (follow-up 1 month-26 years, mean: 17 years) were free from re-operation or intervention. The (extended) end-to-end anastomosis and the subclavian flap method produced the best surgical results. CONCLUSIONS: They suggest the extended end to end anastomosis technique for repair of the aortic arch together with the reconstruction of the associated heart defects in the youngest age if it is possible. The balloon angioplasty of the recoarctation of the aorta produces a good result.

[Ross procedure instead of heart transplantation. Recovery potential of the dysfunctional myocardium in heart failure caused by congenital aortic valve insufficiency]. / Szívátültetés helyett ross-mútét. A diszfunkciós szívizomzat regenerációs képessége veleszületett aortabillentyú-betegség okozta szívelégtelenségben.

UNLABELLED: The authors report a case of a child who presented in advanced valvular heart failure secondary to aortic regurgitation. Due to social circumstances heart transplantation was not a viable option, therefore a high risk pulmonary autograft aortic root replacement (Ross procedure) was performed. Following surgery a delayed but rather gratifying myocardial recovery was observed. CONCLUSION: This case represents the preserved recovery potential of the pediatric myocardium in end stage heart failure.

[Aortic root replacement with pulmonary allograft (Ross procedure) in children. Early results]. / Veleszületett aortabillentyú-betegség kezelése aortagyökpótlással pulmonalis allografttal (Ross-mútét) gyermekkorban. Korai eredmények.

INTRODUCTION: For infants and children with congenital aortic valve disease root replacement with pulmonary allograft (Ross procedure) is the preferred method of choice. PATIENTS/RESULTS: The authors have successfully applied this operation in 12 children (age range from 2.5 to 17 years--mean 9 years, body weight from 12 to 58 kg--mean 46 kg), one of whom has also required a Konno extension for long segment left ventricular outflow tract obstruction. The operation was complicated by early postoperative endocarditis in one case, and the child required redo homograft root replacement on the ninth postoperative day. All patients, including this one survived, and are doing well at present. CONCLUSIONS: In the Hungarian literature this is the first report on the Ross and Konno procedure in children. On the basis of our excellent early results, Ross procedure is the method of choice in aortic valve disease in children.