Importance of microdeletions of chromosomal region 22q11 as a cause of selected malformations of the ventricular outflow tracts and aortic arch: A three-year prospective study☆,☆☆,★,★★
Section snippets
METHODS
All patients who came to Wessex Cardiothoracic Centre from June 1992 to March 1995 were prospectively studied. This regional referral center provides pediatric cardiology and cardiothoracic surgical services to a population of approximately 3 million people. All patients with a new diagnosis of the following cardiac malformations were identified: tetralogy of Fallot with pulmonary stenosis or atresia (with or without systemic-to-pulmonary artery collateral vessels), including those with
Patient characteristics
Fifty children with the selected cardiac malformations came to the Wessex Cardiothoracic Unit during the 34-month period of study. Two cases were identified in fetal life with abnormal echocardiograms. The remaining 48 patients were seen from 1 day to 4 months of age, with all but four having been seen within the first month of life. Cardiac diagnoses were as follows: tetralogy of Fallot with pulmonary stenosis (24 cases), tetralogy of Fallot with pulmonary atresia (12), interrupted aortic arch
DISCUSSION
The pediatric cardiologist caring for an infant with newly diagnosed congenital heart disease is rarely able to offer parents an adequate explanation for the cause of the defect. Recurrence risks are generally provided on the basis of epidemiologic studies rather than of an understanding of the genetic or environmental contributions within an individual family. The recent application of the tools of molecular biology to the study of children with heart disease has provided insights into the
Acknowledgements
We are grateful to Dr. P. J. Scambler, Institute of Child Health, London, for supplying cosmids EO and H748 and primer sequences for the polymorphic marker D22S941 and to Dr. M. Budarf, Children's Hospital of Philadelphia, for supplying cosmid pH17.
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Cited by (108)
Maternal Congenital Heart Disease in Pregnancy
2018, Obstetrics and Gynecology Clinics of North AmericaA novel TBX1 missense mutation in patients with syndromic congenital heart defects
2018, Biochemical and Biophysical Research CommunicationsFetal MRI detects early alterations of brain development in Tetralogy of Fallot
2015, American Journal of Obstetrics and GynecologyCitation Excerpt :Dysfunctional neuroepithelial cells thus may be a common denominator for abnormal brain and heart development in TOF. Syndromic malformations that involve abnormal neural crest development (ie, CATCH 22, DiGeorge syndrome) have been linked to 22q11 microdeletions, which is a chromosomal aberration found in up to 20% of individuals with TOF.18,35,36,39 Further karyotype anomalies, which are linked to TOF and abnormal brain development, include trisomy 13, 18, and 21 and recombinant chromosome 8 syndrome.19,36,37,40
22q11.2 deletion syndrome and complex congenital heart defects
2011, Revista da Associacao Medica BrasileiraCan clinical assessment detect 22q11.2 deletions in patients with cardiac malformations? A review
2011, European Journal of Medical GeneticsCitation Excerpt :In two of these nine studies, all of the patients with a 22q11.2 deletion were detected by clinical assessment [8,33]. Extra-cardiac manifestations were either assessed by a clinical geneticist alone [8] or by a clinical geneticist plus a pediatric cardiologist [33]. Neither of the authors commented on the number of extra-cardiac manifestations that were present in their patients or distinguished between findings of major vs. minor importance.
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From the Wessex Cardiothoracic Centre, Southampton General Hospital, Southampton, Wessex Regional Genetics Service, Princess Anne Hospital, Southampton, and Wessex Regional Genetics Laboratory, Salisbury, United Kingdom
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Supported in part by the Wessex Cardiac Trust (Dr. Daubeney).
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Reprint requests: Steven A. Webber, MBChB, Division of Cardiology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue at De Soto Street, Pittsburgh, PA 15213.
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