Andrea de Zorzi

Ospedale Pediatrico Bambino Gesù, Roma, Latium, Italy

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Publications (17)40.09 Total impact

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    ABSTRACT: Conotruncal defects (CTDs) represent 15-20% of all congenital heart defects. Mutations in a number of genes have been associated with CTD in humans and animal models. We investigated the occurrence and the prevalence of GATA4, NKX2.5, ZFPM2/FOG2, GDF1, and ISLET1 gene mutations in a large cohort of individuals with CTD, including tetralogy of Fallot with or without pulmonary atresia (TOF, 178 patients), double outlet right ventricle (DORV, 13 patients), and truncus arteriosus (11 patients). Denaturing high-performance liquid chromatography (DHPLC) analysis followed by bidirectional sequencing disclosed no putative pathogenic mutation in GATA4, ISLET1, and GDF1 genes. Two novel (Ile227Val, Met544Ile) and one previously reported (Glu30Gly) possibly pathogenic missense variants were identified in the ZFPM2/FOG2 gene in 3 sporadic patients of 202 (1.5%) with CTD, including 1 of 178 (0.6%) with TOF and 2 of 13 (15.4%) with DORV. Mutation analysis also detected one known missense change (Arg25Cys) in NKX2.5 gene in two (1.1%) sporadic patients with TOF. These sequence alterations were found to be absent in 500 population-matched controls. In conclusion, the present results (i) indicate and confirm that mutations in the GATA4, GDF1, and ISLET1 genes are not major determinants in the pathogenesis of TOF, (ii) provide supportive evidence of an association between ZFPM2/FOG2 gene and TOF/DORV, and (iii) provide additional examples of the possible contribution of the Arg25Cys change in the NKX2.5 to a small number of TOF cases.
    Clinical Genetics 08/2011; 80(2):184-90. · 4.25 Impact Factor
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    ABSTRACT: Kawasaki disease (KD) is a systemic vasculitis that mainly affects coronary arteries in children, and requires regular follow-up from the time of diagnosis. To evaluate the feasibility of 64-slice CT angiography (CTA) for follow-up of patients with KD using previously performed invasive catheter coronary angiography (CCA) as reference standard. The study group comprised 12 patients (age 17.6 ± 2.9 years, mean ± SD) with a diagnosis of KD and a previously performed CCA (interval, 32.6 ± 13.5 months) who underwent 64-slice cardiac CTA. The quality of the images for establishing the presence of coronary abnormalities was determined by two observers. The CTA findings were compared with those from the prior CCA. Adequate image quality was obtained in all patients. Mean effective dose for CTA was 6.56 ± 0.95 mSv. CTA allowed accurate identification, characterization and measurement of all coronary aneurysms (n = 32), stenoses (n = 3) and occlusions (n = 9) previously demonstrated by CCA. One patient with disease progression went on to have percutaneous coronary intervention. Coronary lesions were reliably evaluated by 64-slice CTA in the follow-up of compliant patients with KD, reducing the need for repeated diagnostic invasive CCA. Hence, in an adequately selected patient population, the role of CCA could be limited almost only to therapeutic procedures.
    Pediatric Radiology 06/2011; 41(9):1165-73. · 1.57 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    The Pediatric Infectious Disease Journal 07/2010; 29(7):681-2. · 3.57 Impact Factor
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    ABSTRACT: We sought to determine if changes in myocardial physical properties, detected by ultrasound tissue characterization (UTC), are present in asymptomatic children years after an acute episode of Kawasaki disease (KD) and if such changes are related to coronary artery aneurysms (CAs). Myocardial UTC analysis was performed 4.8 + or - 3.4 years after acute KD in 22 patients, mean age 6.6 + or - 3.4 years, with or without CA, who had a normal ECG and normal left ventricular (LV) systolic and diastolic function by echocardiography. Twenty-two age-matched subjects were studied as controls. Cyclic variation of integrated backscatter (cvIBS) and calibrated integrated backscatter (cIBS) were assessed in 16 LV myocardial segments in each patient and control. We found large differences in the UTC data between patients and controls: cvIBS, 7.8 + or - 0.8 vs 8.9 + or - 0.6 dB; cIBS, 28.6 + or - 3.2 vs 25.2 + or - 1.0 dB (P\10-3 for both). The average values of cIBS and cvIBS did not differ significantly between KD patients with and patients without CA or stenosis. In conclusion, UTC analysis demonstrated significant differences in myocardial tissue properties between KD patients and controls, despite similar measures of LV function, independent of coronary artery abnormalities. UTC analysis might improve risk stratification for KD patients.
    Pediatric Cardiology 04/2010; 31(6):766-72. · 1.20 Impact Factor
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    ABSTRACT: GATA4 mutations are found in patients with different isolated congenital heart defects (CHDs), mostly cardiac septal defects and tetralogy of Fallot. In addition, GATA4 is supposed to be the responsible gene for the CHDs in the chromosomal 8p23 deletion syndrome, which is recognized as a malformation syndrome with clinical symptoms of facial anomalies, microcephaly, mental retardation, and congenital heart defects. Thus far, no study has been carried out to investigate the role of GATA4 copy number variations (CNVs) in non-syndromic CHDs. To explore the possible occurrence of GATA4 gene CNVs in isolated CHDs, we analyzed by multiplex ligation-dependent probe amplification (MLPA) a cohort of 161 non-syndromic patients with cardiac anomalies previously associated with GATA4 gene mutations. The patients were mutation-negative for GATA4, NKX2.5, and FOG2 genes after screening with denaturing high performance liquid chromatography. MLPA analysis revealed that normalized MLPA signals were all found within the normal range values for all exons in all patients, excluding a major contribution of GATA4 gene CNVs in CHD pathogenesis.
    Disease markers 01/2010; 28(5):287-92. · 2.14 Impact Factor
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    ABSTRACT: We investigated the prevalence, type, and course of congenital cardiac defects and systemic hypertension in our patients with Williams-Beuren-Beuren syndrome. We reviewed the clinical records of all patients with Williams-Beuren syndrome examined between 1981 and 2006. We identified 150 patients, aged from 7 months to 45 years, with a follow-up from 6 months to 25 years, the mean being 6.4 years. A cardiac anomaly was present in 113 of the 150 patients (75%). Defects were typical in over four-fifths of the group. We found supravalvar aortic stenosis in 73 of 113 patients (64.6%), isolated in 43. Pulmonary stenosis, isolated in 18 cases, was found in 51 of 113 (45.1%), while aortic coarctation and mitral valvar prolapse were each found in 7 (6.2%), 3 of the lesions is isolation. Atypical defects were found in 19 patients, tetralogy of Fallot in 2, atrial septal defects in 4, aortic and mitral valvar insufficiencies in 1 each, bicuspid aortic valves in 2, and ventricular septal defects in 9, 4 of the last being isolated. Systemic hypertension, observed in 33 patients (22%), was poorly controlled in 10. Diagnostic and/or interventional cardiac catheterization was undertaken in 24 patients, with 30 surgical procedures performed in 26 patients. Of the group, 3 patients died. Cardiac defects were present in three-quarters of our patients. Pulmonary arterial lesions generally improved, while supravalvar aortic stenosis often progressed. Atypical cardiac malformations, particularly ventricular septal defects, occurred frequently. Systemic hypertension was found in one-fifth, even in the absence of structural cardiac defects. The short-term mortality was low.
    Cardiology in the Young 12/2009; 19(6):563-7. · 0.95 Impact Factor
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    ABSTRACT: A right aortic arch with a left descending aorta and an aberrant left innominate artery is a rare but recognized vascular anomaly that can result in compression of the trachea and the esophagus. This vascular anomaly has been diagnosed using cardiac catheterization and angiography. Recently, computed tomography and magnetic resonance imaging have been used for noninvasive diagnosis. The aim of this report is to highlight the possibility of echocardiographic diagnosis.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 10/2009; 23(2):221.e5-7. · 2.98 Impact Factor
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    ABSTRACT: Criss-cross heart is a rare congenital cardiac defect characterized by crossing of the atrioventricular valves and of the inflow streams due to the twisting of the ventricles about their long axis. The aetiology of criss-cross heart has not been understood yet. Mice homozygous for Cx43 deficiency show a delay in normal looping of ascending limb of the heart tube, which temporarily retains a more symmetric middle position. Persistence of this condition results in a "criss-cross" configuration, with the atrioventricular cushions rotated 90°, a horizontal muscular ventricular septum, and a parallel course of the endocardial ridges of the outflow tract. We screened the entire coding region of the Cx43 gene in a group of well characterized patients with criss-cross heart, to evaluate whether Cx43 gene mutations cause criss-cross heart in humans. No pathogenic mutation was identified, suggesting that Cx43 mutations are not responsible for criss-cross heart in humans or are not a major cause for this defect.
    International journal of cardiology 04/2009; 144(2):300-2. · 6.18 Impact Factor
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    ABSTRACT: Other authors have demonstrated the ability of three-dimensional (3D) echocardiography to produce "en face" views of anomalies such as atrioventricular valve disease and atrial and ventricular septal defects. Few data exist about the usefulness of 3D images for more complex congenital heart defects and the surgical impact of this relatively new technology. This study, covering a period of 8 months and including 43 young patients affected by complex congenital heart defects, demonstrated that the routine use of 3D echocardiography is feasible and valuable for some types of cardiac defects. In fact, 3D images have provided more detailed anatomic definition of interrelations between structures in about one-third (15/43) of our cases, yielding new insight into the anatomy analogous to what can be derived from examining a heart specimen. Our surgeons found the 3D images particularly helpful for providing a realistic and almost specimen-like preview of the surgical anatomy that facilitates planning of the surgical program.
    Pediatric Cardiology 01/2009; 30(3):293-300. · 1.20 Impact Factor
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    ABSTRACT: The oculo-auriculo-vertebral spectrum (OAVS) is a non-random association of microtia, hemifacial microsomia with mandibular hypoplasia, ocular epibulbar dermoid, and cervical vertebral malformations. Congenital heart defects (CHDs) have been reported in 5-58% of the patients. We analyze the frequency and anatomic features of CHD in a series of 87 patients with OAVS examined between January 1990 and February 2007 with normal chromosomes, ranging in age between 0.1 and 16.8 years. A twin pregnancy occurred in eight cases (dizygotic in six cases and monozygotic in two). CHDs were diagnosed in 28/87 (32%) patients, and classified into categories of postulated developmental mechanisms including 9 (32%) atrial and ventricular septal defects, 11 (39%) conotruncal defects, 4 (14%) targeted growth defects, two (7%) with situs and looping defects, one (4%) with a left-sided obstructive lesion and one (4%) with patent ductus arteriosus. As noted in other series, the most common individual CHDs were ventricular septal defect (six patients) and tetralogy of Fallot (TOF) (classic or with pulmonary atresia) (six patients). Comparing the frequencies of CHDs groups observed in the OAVS patients with the findings of the Emilia-Romagna Registry which ascertained CHDs prevalence in the general population, conotruncal defects, targeted growth defects, and heterotaxia were significantly associated with OAVS.
    American Journal of Medical Genetics Part A 08/2008; 146A(14):1815-9. · 2.30 Impact Factor
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    ABSTRACT: We report on three patients with Costello syndrome (CS) diagnosed during the first year of life and try to outline the clinical characteristics facilitating early recognition of this syndrome, which can now be corroborated by testing the HRAS gene. Phenotypical overlap of CS with Noonan (NS) and cardiofaciocutaneous syndrome (CFCS), particularly in neonatal age, is well known. Diagnostic features useful for recognition of CS in the first year of life are the following: (1) fetal and neonatal macrosomia with subsequent slow growth due to severe feeding difficulties, (2) developmental delay, (3) particularly coarse facial dysmorphisms and gingival hyperplasia, (4) skeletal anomalies as osteoporosis and metaphyseal enlargement, (5) hypertrophic cardiomyopathy (HCM) with asymmetric septal thickening and systolic anterior motion of the mitral valve, and (6) specific atrial arrhythmias. Following a clinical suspect of CS based on specific features, molecular screening of HRAS gene mutations should precede analysis of the other genes in the Ras-MAPK pathway implicated in related disorders with overlapping phenotypes.
    European Journal of Pediatrics 07/2008; 167(6):621-8. · 1.98 Impact Factor
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    ABSTRACT: Ebstein's anomaly is a rare congenital heart defect. Associated lesions are uncommon, and the mortality rates can be as high as 54% during the first month of life. Two cases of severe Ebstein's anomaly with ventricular septal defect are described. It is speculated that this rare association, allowing adequate forward pulmonary blood flow in the neonate, permitted the reported patients to survive the neonatal period, which is the most life-threatening time. The authors propose that the presence of a small ventricular septal defect can be beneficial for such patients, averting the need for surgery during early infancy when the risk is highest.
    Pediatric Cardiology 02/2008; 29(1):217-9. · 1.20 Impact Factor
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    ABSTRACT: The aim of this study was to characterize cardiovascular involvement in a large number of patients with LEOPARD syndrome. Twenty-six patients (age range 0 to 63 years, median age at the time of the study evaluation 17 years) underwent clinical and genetic investigations. Familial disease was ascertained in 9 patients. Nineteen patients (73%) showed electrocardiographic abnormalities. Left ventricular (LV) hypertrophy was present in 19 patients (73%), including 9 with LV outflow tract obstructions; right ventricular hypertrophy was present in 8 patients (30%). Valve (57%) and coronary artery (15%) anomalies were also observed. Single patients showed LV apical aneurysm, LV noncompaction, isolated LV dilation, and atrioventricular canal defect. During follow-up (9.1 +/- 4.5 years), 2 patients died suddenly, and 2 patients had cardiac arrest. These patients had LV hypertrophy. Despite the limited number of subjects studied, genotype-phenotype correlations were observed in familial cases. In conclusion, most patients with LEOPARD syndrome showed LV hypertrophy, often in association with other valvular or congenital defects. A spectrum of underrecognized cardiac anomalies were also observed. Long-term prognosis was benign, but the occurrence of 4 fatal events in patients with LV hypertrophy indicates that such patients require careful risk assessment and, in some cases, consideration for prophylaxis against sudden death.
    The American Journal of Cardiology 09/2007; 100(4):736-41. · 3.21 Impact Factor
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    ABSTRACT: Tetralogy of Fallot associated with the atrioventricular canal defect has been usually reported in association with Down syndrome. The aim of the present study was to describe the cardiac aspects and the genetic anomalies in children with this association of heart defects. We identified 64 patients with atrioventricular canal defect tetralogy of Fallot. All children underwent complete cardiovascular, clinical phenotypic and genetic evaluation. A genetic syndrome or extracardiac anomalies were found in 56 patients (87.5%). Down syndrome (43 patients, 67.2%) was the most frequent genetic diagnosis. Other syndromes were 8p deletion, trisomy 13, duplication 5p, cranio-cerebello-cardiac syndrome, Cantrell syndrome, CHARGE association, VACTERL association, and DiGeorge syndrome related to maternal diabetes. No patients in our series had 22q11 deletion. Tetralogy of Fallot with extreme dextroposition of the aorta was found in seven patients (only one with Down syndrome). Additional cardiac malformations were present in 23 patients (only 11 with Down syndrome). The association between atrioventricular canal defect and tetralogy of Fallot represents a cardiac phenotype with strong genetic characteristics. For this reason, a careful genetic examination is required. Our study confirms the high prevalence of Down syndrome, but also reveals a significant genetic heterogeneity. Additional cardiac defects are prevalent in patients without Down syndrome.
    Clinical dysmorphology 05/2006; 15(2):65-70. · 0.47 Impact Factor
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    ABSTRACT: LEOPARD syndrome (LS) is an autosomal dominant syndrome characterized by multiple lentigines and café-au-lait spots, electrocardiographic-conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormalities of the genitalia in males, retardation of growth, and deafness. LS shares many features with Noonan syndrome (NS), in which lentigines and deafness are usually not present. Molecular studies have shown that LS and NS are allelic disorders, caused by different missense mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at chromosome 12q22-qter. The clinical diagnosis of LS is generally difficult in the first months of life because the distinctive lentigines are generally not present at birth and develop during childhood. From January 2002 to December 2004, we suspected LS clinically in 10 patients admitted to our genetic counseling services in the first 12 months of life. A PTPN11 gene mutation was detected in 8/10 (80%) patients. In one patient without a PTPN11 mutation a subsequent clinical diagnosis of neurofibromatosis type 1 (NF1) was made, following the evaluation of the mother, who had previously undiagnosed classic NF1. The age of LS patients with PTPN11 mutation ranged between 1 and 11 months (mean age +/- SD 7.5 +/- 3.96 months). Review of the clinical characteristics of patients with LS confirmed by molecular study during the first year of life demonstrates that the diagnosis of LS in the first months of age can be clinically suspected in patients presenting with three main features, that is, characteristic facial features (100%), hypertrophic cardiomyopathy (HCM) (87%), and cafe-au-lait spots (75%). Characteristic facial features can be mild or severe, and consist of hypertelorism, downslanting palpebral fissures, ptosis, and dysmorphic ears. The clinical suspicion of LS may be confirmed by molecular screening for PTPN11 mutations. An early diagnosis of the disease is useful for the prospective care of associated medical problems and for precise genetic counseling.
    American Journal of Medical Genetics Part A 05/2006; 140(7):740-6. · 2.30 Impact Factor
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    ABSTRACT: Familial recurrence of congenitally corrected transposition of the great arteries (CCTGA) is considered uncommon. Most of the previous familial studies involved a small number of patients and referred to all situs and looping anomalies including single ventricle, heterotaxia, and other cardiac defects different from CCTGA. We performed a large, consecutive clinical case series study in order to detect the recurrence of congenital heart defects in families of children with the classic form of CCTGA. From January 1997 through December 2004, 102 consecutive patients with CCTGA were evaluated in four institutions. There were 59 male (57.8%) and 43 female (42.2%). Mean age was 8.6 +/- 7.8 years. Eighty-eight patients (86.3%) had situs solitus of the atria, 14 (13.7%) situs inversus. The cardiac and extracardiac anomalies among relatives and the patterns of familial recurrence were investigated. Relatives with congenital heart defects were found in 16/102 families (15.7%). Transposition of the great arteries (TGA) was the most common recurrent defect (6/102 families). Consanguinity was identified in the parents of three probands. Six probands had an unaffected twin-sib. Recurrence risks for congenital heart defects were calculated at 5.2% (6/116) for siblings. In conclusion, CCTGA is not always sporadic in families. The pattern of inheritance, the presence of consanguinity among parents and the recurrence of situs inversus could suggest, in some families, an autosomal recessive mechanism with similarities with that occurring in some pedigrees with heterotaxia. The recurrence of TGA and CCTGA in the same family suggests a pathogenetic link between these two anatomically different malformations.
    American Journal of Medical Genetics Part A 09/2005; 137(2):176-80. · 2.30 Impact Factor
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    ABSTRACT: The majority of nonsyndromic congenital heart defects (CHDs) are considered to follow a multifactorial model of inheritance. Multiple family members affected by CHD can occasionally be detected, and the involvement of several genetic loci interacting with environmental factors is suspected to be implicated. The DiGeorge/velo-cardio-facial syndrome related to microdeletion 22q11.2 (del22) is a genetic condition associated with CHD in most of the cases. We report here on five pedigrees of patients with del22, showing occurrence of nonsyndromic CHD in a first-degree relative of the proband case. Familial aggregation of syndromic and nonsyndromic CHD as observed in our series is to be considered as an unusual pattern of recurrence. The interaction between several different genes and environmental factors, a familial susceptibility predisposing to a specific cardiac malformation, or chance association can all be hypothesized searching an explanation for these particular observations.
    American Journal of Medical Genetics Part A 05/2005; 134A(2):158-64. · 2.30 Impact Factor

Publication Stats

187 Citations
40.09 Total Impact Points


  • 2005–2011
    • Ospedale Pediatrico Bambino Gesù
      • Department of Pediatric Cardiology and Cardiac Surgery
      Roma, Latium, Italy
  • 2009–2010
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      Giovanni Rotondo, Apulia, Italy
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 2005–2007
    • Sapienza University of Rome
      • • Laboratory of Experimental Medicine and Pathology Environmental
      • • Department of Experimental Medicine
      Roma, Latium, Italy