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Biomedical subjects

A Giannotti

Publications and source records attributed to A Giannotti.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pulmonary atresia with ventricular septal defect: prevalence of deletion 22q11 in the different anatomic patterns.

BACKGROUND: Pulmonary atresia with ventricular septal defect (PA-VSD) is one of the most common cardiac defects associated with DiGeorge syndrome. The pattern of the pulmonary circulation determines the complexity of this type of heart disease. The aim of this study was to establish the prevalence of DiGeorge syndrome with deletion 22q11 in patients with simple and complex PA-VSD. METHODS: Since 1993 we have studied 128 consecutive patients affected by PA-VSD. In 90 of our patients the PA-VSD was considered "simple" (group I), because it was not associated with any other cardiac defects. In the other 38 children the PA-VSD was considered "complex" (group II) owing to the presence of heterotaxia, tricuspid atresia, a double-inlet left ventricle, transposition of the great arteries and congenitally corrected transposition of the great arteries. RESULTS: In group I, 38 patients (42%) had genetic syndromes or major extracardiac anomalies; deletion 22q11 was detected in 31% of cases. Major aortopulmonary collateral arteries were present in 50% of group I patients and in 57% of those with deletion 22q11. In group II, 10 patients (26%) had genetic syndromes or major extracardiac anomalies but none had deletion 22q11 (p < 0.005); in no case was the presence of major aortopulmonary collateral arteries observed (p < 0.005). CONCLUSIONS: PA-VSD is an anatomically and morphogenetically heterogeneous disease: in the setting of DiGeorge syndrome or velocardiofacial syndrome, PA-VSD is associated with a peculiar cardiac pattern and is due to deletion 22, whereas in case of nonsyndromic PA-VSD or when this disease is associated with different syndromes or with other types of cardiac defects, it is due to other morphogenetic mechanisms.

Child Welfare↗
PubMed2000

Heterotaxy with left atrial isomerism in a patient with deletion 18p.

We report on a female infant with partial deletion of the short arm of chromosome 18 (del 18p) and heterotaxy with left atrial isomerism. Congenital heart defect (CHD) is found in 10% of the literature reports. Interestingly, situs abnormalities have been diagnosed in four patients with del 18p, including ours. This finding could imply that a locus or loci involved in the development of normal body situs lies within this chromosomal region. Del 18p must be consid- ered when evaluating a patient with phenotypic anomalies and CHD in lateralization defects.

Chromosome Deletion↗
PubMed2000

Deletion of a 5-cM region at chromosome 8p23 is associated with a spectrum of congenital heart defects.

BACKGROUND: Cytogenetic evidence suggests that the haploinsufficiency of > or =1 gene located in 8p23 behaves as a dominant mutation, impairing heart differentiation and leading to a wide spectrum of congenital heart defects (CHDs), including conotruncal lesions, atrial septal defects, atrioventricular canal defects, and pulmonary valve stenosis. An 8p heart-defect-critical region was delineated, and the zinc finger transcription factor GATA4 was considered a likely candidate for these defects. We narrowed this region and excluded a major role of GATA4 in these CHDs. METHODS AND RESULTS: We studied 12 patients (7 had CHD and 5 did not) with distal 8p deletions from 9 families by defining their chromosome rearrangements at the molecular level by fluorescent in situ hybridization and short-tandem repeat analysis. Subjects with 8p deletions distal to D8S1706, at approximately 10 cM from the 8p telomere, did not have CHD, whereas subjects with a deletion that included the more proximal region suffered from the spectrum of heart defects reported in patients with 8p distal deletions. The 5-cM critical region is flanked distally by D8S1706 and WI-8327, both at approximately 10 cM, and proximally by D8S1825, at 15 cM. Neither GATA4 nor angiopoietin-2 (ANGPT2; a gene in 8p23 involved in blood vessel formation) were found to be deleted in some of the critical patients. We also found that CHDs are not related to the parental origin of deletion. CONCLUSIONS: Haploinsufficiency for a gene between WI-8327 and D8S1825 is critical for heart development. A causal relationship does not seem to exist between GATA4 and ANGPT2 haploinsufficiency and CHDs.

Adolescent↗
PubMed2000

Novel 7-DHCR mutation in a child with Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by minor facial anomalies, mental retardation, and multiple congenital abnormalities. Biochemically, the disorder is caused by deficient activity of 7-dehydrocholesterol reductase, which catalyzes the reduction of the Delta7 double bond of 7-dehydrocholesterol to produce cholesterol. Recently, mutations in the gene encoding 7-dehydrocholesterol reductase (7DHCR) were found to cause SLOS. We report the first molecular characterization of an Italian SLOS patient. Interestingly, his paternal 7DHCR allele, of Arab origin, harbored a novel P329L mutation which in combination with a maternal splice-site (IVS8-1 G>C) mutation resulted in a relatively milder phenotype.

Abnormalities, Multiple↗
PubMed2000

Clinical and cardiorespiratory assessment in children with Down syndrome without congenital heart disease.

OBJECTIVE: To assess the clinical and functional status of a young Down syndrome (DS) population without congenital heart disease. DESIGN: Prospective study of children with DS and control subjects. SETTING: Bambino Gesù Children's Hospital, Rome, Italy. PARTICIPANTS AND METHODS: Forty-two children with DS (mean +/- SD age, 9.8 +/- 3.6 years) underwent genetic, clinical, neuropsychological (IQ), and cardiorespiratory evaluation. Cardiorespiratory fitness was assessed with a treadmill test and a lung function test to determine forced vital capacity, first-second forced expiratory volume, and peak expiratory flow. Data were expressed as a percentage of the predicted values for control children. To assess cooperation during exercise testing, we devised a compliance scale assigning a score according to the subjects' ability to understand instructions, ability to walk and run as required, and need for vocal encouragement. RESULTS: Eighteen (43%) of 42 children with DS were obese, 10 (24%) were short, and 17 (40%) had microcephaly. On the Leiter International Performance Scale, 2 of 35 subjects had a normal IQ score (80-120); all others had low IQ scores (79 to <40). Five subjects did not undergo cardiorespiratory assessment. Eighteen of 37 subjects completed lung function tests: the results for 10 were unremarkable, and results from 8 revealed reduced forced vital capacity because of poor compliance. The subjects tested had low exercise tolerance (mean +/- SD tolerance percentage, 61% +/- 12%), mild tachycardia (maximal heart rate, 91% +/- 4%), and a mild hypertensive response (maximal blood pressure, 89% +/- 8%). Compliance scores correlated significantly with exercise time and age but not with IQ. CONCLUSIONS: Clinical and cardiorespiratory assessment is feasible in subjects with DS without congenital heart disease and should be useful in gauging their fitness level for safe physical activity.

Adolescent↗
PubMed2000

Familial recurrence of nonsyndromic interrupted aortic arch and truncus arteriosus with atrioventricular canal.

BACKGROUND: Multifactorial inheritance is probably involved in most cases of nonsyndromic conotruncal heart defects (CHDs), but Mendelian transmission is often suspected. RESULTS: We report on a family with recurrence of nonsyndromic CTHD in two double first cousins; i.e., two brothers married two sisters. One of the cousins (case 1) had interrupted aortic arch (IAA) type B, while the other one (case 2) had truncus arteriosus (TA) with atrioventricular canal defect (AVCD). CONCLUSIONS: Our family further supports monogenic inheritance of CTHDs. In addition, the presence of TA associated with AVCD in one of the patients confirms the higher occurrence of CTHD in families with complex TA. The absence of 22q11 microdeletion (del22q11) in our patients, as in several literature reports of familial CTHDs, supports the existence of genes different to those located on chromosome 22q11 which could be implicated in the pathogenesis of CTHDs.

Aorta, Thoracic↗
PubMed2000

Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome.

The neurotrophin nerve growth factor (NGF) is a major regulator of peripheral and central nervous system development. Serum NGF was measured in normally developing control children (n=26) and in individuals affected by congenital syndromes associated with learning disability: either Williams syndrome (WS; n=12) or Down syndrome (DS; n=21). Participants were assessed at three distinct developmental stages: early childhood (2 to 6 years), childhood (8 to 12 years), and adolescence (14 to 20 years). A sample was taken only once from each individual. Serum NGF levels were markedly higher in participants with WS, than DS and control participants. In addition, different developmental profiles emerged in the three groups: while in normally developing individuals NGF levels were higher in early childhood than later on, children with WS showed constantly elevated NGF levels. When compared to control participants, those with DS showed lower NGF levels only during early childhood. Neuropsychological assessment confirmed previously reported differences among the three groups in the development of linguistic/cognitive abilities. Some features of individuals with WS, such as hyperacusis and hypertension, could be related to high-circulating NGF levels.

Adolescent↗
PubMed2000

Short arm rearrangements of sex chromosomes with haploinsufficiency of the SHOX gene are associated with Leri-Weill dyschondrosteosis.

Twelve patients with different features of Turner syndrome, and with Xp and Yp rearrangements involving the pseudoautosomal region (PAR1) are described. In all patients, FISH analysis showed loss of one copy of the Short Stature Homeobox (SHOX)-containing gene. Ten patients had short stature and one disproportionate (mesomelic) normal stature, while the last one had normal stature. Skeletal abnormalities, including shortened ulna, were detected in nine subjects, and in six of them Madelung deformity was observed. These clinical data indicated a genotype phenotype correlation between haploinsufficiency of SHOX, and short stature and skeletal abnormalities.

Adolescent↗
PubMed2000

T cell receptor repertoire and function in patients with DiGeorge syndrome and velocardiofacial syndrome.

DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are associated with chromosome 22q11.2 deletion. Limited information is available on the T cell receptor (TCR) Vbeta repertoire. We therefore investigated TCR Vbeta families in lymphocytes isolated from blood and thymic samples of seven patients with DGS and seven patients with VCFS, all with 22q11.2 deletion. We also studied activities related to TCR signalling including in vitro proliferation, anti-CD3-induced protein tyrosine phosphorylation, and susceptibility to apoptosis. Reduced CD3+ T cells were observed in most patients. Spontaneous improvement of T cell numbers was detected in patients, 3 years after the first study. Analysis of CD4+ and CD8+ TCR Vbeta repertoire in peripheral and thymic cells showed a normal distribution of populations even if occasional deletions were observed. Lymphoproliferative responses to mitogens were comparable to controls as well as anti-CD3-induced protein tyrosine phosphorylation. Increased anti-CD3-mediated apoptosis was observed in thymic cells. Our data support the idea that in patients surviving the correction of cardiac anomalies, the immune defect appears milder than originally thought, suggesting development of a normal repertoire of mature T cells.

Abnormalities, Multiple↗
PubMed2000

Obesity and WAGR syndrome.

We describe a 15-year-old boy with WAGR syndrome and obesity and suggest that obesity should be added to the WAGR spectrum. It is also suggested that a putative gene for obesity might be located within the 11p13 band.

Adolescent↗
PubMed1999

Deletion 22q11 in patients with interrupted aortic arch.

In our series of 27 children with various types of interruption of the aortic arch (IAA), deletion 22q11 is prevalent in patients with simple IAA type B, and is absent in patients with IAA type A and in those with associated additional major cardiac defects. Anomalies of the infundibular septum should be considered a characteristic aspect of children with IAA and deletion 22q11.

Abnormalities, Multiple↗
PubMed1999

Atrioventricular canal defect without Down syndrome: a heterogeneous malformation.

The atrioventricular canal defect (AVCD) is one of the congenital heart defects most frequently associated with extracardiac anomalies. The association of AVCD with Down syndrome and heterotaxy has been studied extensively. However, little information is available about the prevalence of genetic syndromes and additional cardiac malformations in patients with AVCD and visceroatrial situs solitus without Down syndrome. This paper reviews the genetic and cardiologic characteristics of patients with non-Down AVCD and situs solitus in the literature and our series of 203 consecutive patients. In our experience, 132 (65%) of the patients have nonsyndromic AVCD, while 71 (35%) have non-Down syndromic AVCD. Chromosomal imbalances were detected in 7 cases (3%), Mendelian syndromes or associations in 44 (22%), and extracardiac anomalies without an identifiable syndrome in 20 (10%). Deletion 8p is prevalent among those with chromosomal imbalances. Noonan, Ellis-van Creveld, oro-faciodigital, Smith-Lemli-Opitz syndromes and VACTERL cases are frequent among patients with recognizable or identifiable nonchromosomal conditions. Based on this analysis of the type of AVCD and prevalence of associated cardiac anomalies in the different groups of patients, we found that: 1) the complete form is prevalent in patients with chromosomal imbalances; 2) the complete form is more frequently associated with additional cardiac defects, mainly left side obstructive lesions; and 3) additional cardiac anomalies are prevalent in syndromic patients. In conclusion, AVCD is a congenital heart defect with great variability in the anatomic patterns and heterogeneity of causes also in the subset without Down syndrome and without heterotaxy. The peculiar anatomic subtypes of this cardiac defect are associated with specific genetic conditions.

Chromosome Aberrations↗
PubMed1999

Cardiac malformations in patients with oral-facial-skeletal syndromes: clinical similarities with heterotaxia.

Oral-facial-skeletal (OFS) syndromes include short rib-polydactyly (SRP) and oral-facial-digital (OFD) syndromes. Congenital heart defect (CHD), mainly atrioventricular canal defect (AVCD), is a cardinal finding in the Ellis-van Creveld (EVC) syndrome, but it occurs only occasionally in other SRP and OFD syndromes. The cardiac characteristics of all patients with OFS syndromes evaluated at our hospital from January 1986 to April 1997 were analyzed and compared with published reports. Ten patients with EVC syndrome, one with McKusick-Kaufman syndrome, and one with OFD syndrome type II had AVCD. Eight patients (67%) had a common atrium, eight (67%) a persistent left superior vena cava (LSVC) draining into the left atrium because of an unroofed coronary sinus in five (42%), and left-sided obstructive lesions in three (25%). One patient with EVC syndrome had AVCD, common atrium, double outlet right ventricle, persistent LSVC associated with "asplenia syndrome," visceral heterotaxia, and right isomerism. The combination of CHDs found in the personal series of OFS syndromes suggests pathogenetic similarity with heterotaxia syndromes. Published results also corroborate the association between OFS syndromes and CHDs usually occurring in heterotaxia. Molecular studies could shed light on the genetic mechanisms implicated in the cause of the OFS and heterotaxia syndromes.

Ellis-Van Creveld Syndrome↗
PubMed1999

Atrioventricular canal defect and hypoplastic left heart syndrome as discordant congenital heart defects in twins.

We report on a twin pair presenting with atrioventricular canal defect (AVCD) with right ventricular dominance in one twin, and classic hypoplastic left heart syndrome (HLHS) in the other. According to the developmental-mechanistic approach, AVCDs belong to the group of extracellular matrix abnormalities, whereas classic HLHS is included among flow lesions. Twin pairs with congenital heart defect (CHD) generally have concordant defects by mechanistic group. The occurrence of AVCD and classic HLHS in twins or siblings has never been reported. Interestingly, hypoplasia of the left ventricle is the anatomic characteristic which unifies the discordant CHDs observed in our twins. The occurrence of CHD in both members of the twin pair implies a strong influence of genetic factors. At present, the genetic basis determining the different cardiac phenotypes observed in our twins is unknown. The report of these peculiar associations may be useful to stimulate further studies and shed light on the etiology of CHDs.

Child, Preschool↗