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Common Atrioventricular Canal. CONGENIT HEART DIS 2022. [DOI: 10.1016/b978-1-56053-368-9.00011-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Versacci P, Pugnaloni F, Digilio MC, Putotto C, Unolt M, Calcagni G, Baban A, Marino B. Some Isolated Cardiac Malformations Can Be Related to Laterality Defects. J Cardiovasc Dev Dis 2018; 5:jcdd5020024. [PMID: 29724030 PMCID: PMC6023464 DOI: 10.3390/jcdd5020024] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 04/21/2018] [Accepted: 04/25/2018] [Indexed: 12/22/2022] Open
Abstract
Human beings are characterized by a left–right asymmetric arrangement of their internal organs, and the heart is the first organ to break symmetry in the developing embryo. Aberrations in normal left–right axis determination during embryogenesis lead to a wide spectrum of abnormal internal laterality phenotypes, including situs inversus and heterotaxy. In more than 90% of instances, the latter condition is accompanied by complex and severe cardiovascular malformations. Atrioventricular canal defect and transposition of the great arteries—which are particularly frequent in the setting of heterotaxy—are commonly found in situs solitus with or without genetic syndromes. Here, we review current data on morphogenesis of the heart in human beings and animal models, familial recurrence, and upstream genetic pathways of left–right determination in order to highlight how some isolated congenital heart diseases, very common in heterotaxy, even in the setting of situs solitus, may actually be considered in the pathogenetic field of laterality defects.
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Affiliation(s)
- Paolo Versacci
- Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy.
| | - Flaminia Pugnaloni
- Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy.
| | - Maria Cristina Digilio
- Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital and Research Institute, 00165 Rome, Italy.
| | - Carolina Putotto
- Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy.
| | - Marta Unolt
- Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy.
| | - Giulio Calcagni
- Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital and Research Institute, 00165 Rome, Italy.
| | - Anwar Baban
- Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital and Research Institute, 00165 Rome, Italy.
| | - Bruno Marino
- Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy.
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Chaix MA, Andelfinger G, Khairy P. Genetic testing in congenital heart disease: A clinical approach. World J Cardiol 2016; 8:180-191. [PMID: 26981213 PMCID: PMC4766268 DOI: 10.4330/wjc.v8.i2.180] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Revised: 10/16/2015] [Accepted: 12/11/2015] [Indexed: 02/06/2023] Open
Abstract
Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.
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Calcagni G, Digilio MC, Sarkozy A, Dallapiccola B, Marino B. Familial recurrence of congenital heart disease: an overview and review of the literature. Eur J Pediatr 2007; 166:111-6. [PMID: 17091259 DOI: 10.1007/s00431-006-0295-9] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2006] [Revised: 08/21/2006] [Accepted: 08/22/2006] [Indexed: 01/09/2023]
Abstract
Familial recurrence is one of the classic patterns for the clinical presentation of congenital heart disease (CHD). In recent years, many groups studied empiric recurrence risk in these heart defects, and the aim of this review was to analyse the patterns of inheritance detected in different types of CHD, including atrioventricular canal defect, tetralogy of Fallot, transposition of the great arteries, left-sided obstructions and atrial septal defect. These studies may influence clinical practise guidelines through accurate genetic counselling, but also, they may have important implications in the knowledge of genetic and pathogenetic mechanisms of CHD.
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Affiliation(s)
- Giulio Calcagni
- Pediatric Cardiology, Department of Pediatrics, University La Sapienza, Rome, Italy
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Digilio MC, Marino B, Giannico S, Giannotti A, Dallapiccola B. Atrioventricular canal defect and hypoplastic left heart syndrome as discordant congenital heart defects in twins. TERATOLOGY 1999; 60:206-8. [PMID: 10508973 DOI: 10.1002/(sici)1096-9926(199910)60:4<206::aid-tera4>3.0.co;2-a] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
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.
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Affiliation(s)
- M C Digilio
- Department of Medical Genetics, Bambino Gesù Hospital, 00165 Rome, Italy
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Geva T, Ayres NA, Pignatelli RH, Gajarski RJ. Echocardiographic Evaluation of Common Atrioventricular Canal Defects: A Study of 206 Consecutive Patients. Echocardiography 1996; 13:387-400. [PMID: 11442945 DOI: 10.1111/j.1540-8175.1996.tb00910.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
An accurate echocardiographic evaluation of common atrioventricular canal (CAVC) requires in-depth knowledge of the wide spectrum of morphological and physiological variations in this group of anomalies. In order to evaluate the incidence and morphological distribution of AV canal defects in a large series of patients and to define a systematic approach to the echocardiographic examination, we reviewed the echocardiograms of 206 consecutive patients with CAVC studied at Texas Children's Hospital over a 32-month period. The complete form of CAVC was most common (68.4%) and presented at an earlier age (mean +/- SD: 1.6 +/- 2.4 months). A partial AV canal (ostium primum atrial septal defect [ASD]) was found in 42 patients (20.4%) and their age at presentation was higher (9.2 +/- 10 months). Twenty-three patients (11.2%) had a transitional AV canal. Down syndrome was diagnosed in 34% of patients, the majority of whom (79%) had a complete CAVC. Associated malformations were found in 46% of patients: anomalies of the conotruncus were most frequent (18%), followed by secundum ASD (14.1%), anomalous pulmonary venous connection (11.2%), and heterotaxy syndrome (11.2%). Subaortic obstruction and mitral stenosis were less common. The AV canal was unbalanced in 14.1% of patients, with the right ventricular dominant form being more common than the left ventricular dominant form (10.7% and 3.4%, respectively). Based on our experience, we developed a systematic, segment-by-segment approach to the echocardiographic examination in infants with CAVC. Together with detailed anatomical information, Doppler evaluation provides crucial hemodynamic information that allows planning of surgical repair. (ECHOCARDIOGRAPHY, Volume 13, July 1996)
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Affiliation(s)
- Tal Geva
- Department of Cardiology, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115
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Disegni E, Pierpont ME, Bass JL, Kaplinsky E. Two-dimensional echocardiography in detection of endocardial cushion defect in families. Am J Cardiol 1985; 55:1649-52. [PMID: 4003317 DOI: 10.1016/0002-9149(85)90998-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Emanuel R, Marcomichelakis J, Withers R, O'Brien K. Asymmetric septal hypertrophy and hypertrophic cardiomyopathy. Heart 1983; 49:309-16. [PMID: 6681979 PMCID: PMC481305 DOI: 10.1136/hrt.49.4.309] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
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Emanuel R, Somerville J, Inns A, Withers R. Evidence of congenital heart disease in the offspring of parents with atrioventricular defects. BRITISH HEART JOURNAL 1983; 49:144-7. [PMID: 6824534 PMCID: PMC481276 DOI: 10.1136/hrt.49.2.144] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Fifty-two of the 56 offspring from 90 patients with proven atrioventricular defects were examined. There were five with congenital heart disease. The defects were concordant in three and discordant in two. The mother was the affected propositus in all cases. In this relatively small sample the incidence of congenital heart disease in the offspring of parents with atrioventricular defects was 9.6%, or 14.3% if only the female propositi were considered. This is a much higher figure than that reported for the simple forms of isolated congenital heart disease.
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Emanuel R, Withers R, O'Brien K, Ross P, Feizi O. Congenitally bicuspid aortic valves. Clinicogenetic study of 41 families. Heart 1978; 40:1402-7. [PMID: 737099 PMCID: PMC483586 DOI: 10.1136/hrt.40.12.1402] [Citation(s) in RCA: 68] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The families of 41 patients with surgically proved isolated bicuspid aortic valves were examined. There were 275 first degree relatives of whom 220 were living, and 188 (85.5%) of these were examined. Seven first degree relatives were found to have aortic valve disease, and in a further 11 there was 'doubtful' evidence of bicuspid aortic valves. In 6 families there was more than 1 affected member and in an additional 7 families there was 1 or more 'doubtful' first degree relative. The minimum family incidence was therefore 14.6 per cent, or 31.7 per cent if 'doubtful' cases were included. The inheritance is most probably multifactorial, but occasionally the condition may occur as an autosomal dominant. The difficulties of diagnosing bicuspid aortic valves before the development of obstruction of left ventricular outflow were encountered and are discussed. The association of a bicuspid aortic valve with asymmetric septal hypertrophy, hypertrophic cardiomyopathy, and Marfan's syndrome was also noted.
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Nora JJ, Nora AH. The evolution of specific genetic and environmental counseling in congenital heart diseases. Circulation 1978; 57:205-13. [PMID: 338196 DOI: 10.1161/01.cir.57.2.205] [Citation(s) in RCA: 134] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Emanuel R, Ng RA, Marcomichelakis J, Moores EC, Jefferson KE, MacFaul PA, Withers R. Formes frustes of Marfan's syndrome presenting with severe aortic regurgitation. Clinicogenetic study of 18 families. BRITISH HEART JOURNAL 1977; 39:190-7. [PMID: 836734 PMCID: PMC483215 DOI: 10.1136/hrt.39.2.190] [Citation(s) in RCA: 34] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Eighteen patients who presented with severe aortic regurgitation and dilatation of the ascending aorta were found to be formes frustes of Marfan's syndrome and formed the basis for this clinicogenetic study. All had aortic valve replacement and reconstruction of part of the ascending aorta. The diagnosis was confirmed by histological examination of the aortic tissue. There were 126 first degree relatives; 85 were living and 67 (78-8%) of these were examined. Limited information was available about 32 of the 41 relatives who had died. No relative had the classical clinical features of Marfan's syndrome but stigmata of the disease were found in 25 (37-3%) of the 67 first degree relatives examined. In 21, the abnormality was confined to the cardiovascular system, the skeleton, or the eye, but in 4, abnormalities involved 2 systems. Cardiovascular abnormalities affecting the aortic valve or aortic wall were present in 6 (9-0%) of the 67 first degree relatives examined. One or more of the skeletal indices measured (height-span difference, metacarpal index, phalangeal index) was abnormal in 18 (26-9%) and ocular abnormalities were found in 5 of 51 (9-8%) examined. There were no relatives with dislocation of the lens or iridodonesis. Using strict diagnostic criteria, a minimum of 37-3 per cent of the first degree relatives examined were affected; this involved 12 of the 18 families studied. There was nothing in our data to suggest that the formes frustes of the disease had a different mode of inheritance from the classical syndrome.
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Abstract
Families of 100 patients with coarctation of the aorta and 50 controls for age, sex, and social status were studied to assess the influence of genetic and environmental variables in the aetiology. A tendency to familial aggregation of the condition and other congenital heart defects compatible with multifactorial inheritance was discerned. Recurrence risk for sibs is approximately 1 in 200 for coarctation of the aorta, and 1% for any form of congenital heart defect. The heritability of coarctation is estimated at 58%. The tendency for other non-cardiac defects to occur in the patients with coarctation does not appear in their sibs and is not so pronounced as in some other congenital heart conditions. Of the several environmental variables examined, there was no definitive association with any other than season of birth, which implies a possible association with maternal infection; there is also a suggestion of a paternal age effect, but these require investigation in a prospective survey.
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Anderson RC. Fetal and infant death, twinning and cardiac malformations in families of 2,000 children with and 500 without cardiac defects. Am J Cardiol 1976; 38:218-24. [PMID: 952265 DOI: 10.1016/0002-9149(76)90153-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Analysis of family data on 2,000 children with a congenital cardiac malformation of unknown origin and 500 with an innocent murmur showed the incidence of twinning in probands, siblings and parents to be the same as in the general population. The mothers in the two groups of probands had the same incidence of spontaneous abortions and stillbirths. There was a small increase in infant mortality in siblings of probands with a cardiac malformation, but this could be accounted for by the increased incidence of cardiac malformations. The latter occurred in 1.4 percent of all siblings and in 1.7 percent of later born siblings. Complete concordance for malformation type occurred in 31 percent of affected siblings and 46 percent of affected parents, and partial concordance occurred in an additional 21 and 8 percent, respectively. Combined direct and indirect observations and calculations indicate that the risk of recurrent cardiac malformations is 1.4 to 3 percent in families in which one child was born with a cardiac malformation of unknown origin; no significant difference was evident for the various cardiac malformations.
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Emanuel R, O'Brien K, Somerville J, Jefferson K, Hegde M. Association of secundum atrial septal defect with abnormalities of atrioventricular conduction or left axis deviation. Genetic study of 10 families. BRITISH HEART JOURNAL 1975; 37:1085-92. [PMID: 1191421 PMCID: PMC482923 DOI: 10.1136/hrt.37.10.1085] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
A genetic analysis was made of 10 families in which the propositi had a secundum atrial septal defect associated with abnormal atrioventricular conduction (first, second, or third degree heart block) or unexplained left axis deviation or a combination of these conduction disturbances. Diagnostic information was available on 51 (81%) of the first degree relatives. Three of the families appeared to be examples of a new syndrome which, with variable expression, was inherited as a non-sex-linked autosomal dominant. The main features were a secundum atrial septal defect; disease of the conducting tissue, which in some cases was progressive; unexplained left axis deviation; and unexpected death. These families did not seem to be examples of the Holt-Oram syndrome, for the upper limbs were clinically and radiologically normal in the 19 members examined. The importance of recognizing this syndrome is the occurrence of progressive disease of the conducting tissue and the risk of sudden death. When, therefore, unexplained left axis deviation or prolonged atrioventricular conduction is found in association with a secundum atrial septal defect all available relatives should be examined. In the remaining seven families there was only one affected first degree relative out of 39 examined. He was the son of one of the propositi and had paroxysmal coronary sinus rhythm with an intact atrial septum.
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Abstract
Of 109 cases of atrial septal defect, cases with an isolated defect (92 cases) showed a female preponderance (sex ratio 0·64), but there was a higher risk to the sibs of the male patients, suggesting a multifactorial mechanism. Dermatoglyphs showed a large number of whorls on the fingers. In 17 cases there were multiple malformations, such as Holt-Oram syndrome (hypoplastic and triphalangic thumb, with ostium secundum atrial septal defect), polydactyly plus ostium primum defect, and tracheo-oesophageal fistula.
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