Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the Literature
The use of clinical genetics evaluations and testing for infants with congenital heart defects (CHDs) is subject to practice variation. This single-institution cross-sectional study of all inpatient infants with severe CHDs evaluated 440 patients using a cardiovascular genetics service (2014–2019)....
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/8/1244 |
| _version_ | 1797523776892567552 |
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| author | Benjamin M. Helm Benjamin J. Landis Stephanie M. Ware |
| author_facet | Benjamin M. Helm Benjamin J. Landis Stephanie M. Ware |
| author_sort | Benjamin M. Helm |
| collection | DOAJ |
| description | The use of clinical genetics evaluations and testing for infants with congenital heart defects (CHDs) is subject to practice variation. This single-institution cross-sectional study of all inpatient infants with severe CHDs evaluated 440 patients using a cardiovascular genetics service (2014–2019). In total, 376 (85.5%) had chromosome microarray (CMA), of which 55 (14.6%) were diagnostic in syndromic (N = 35) or isolated (N = 20) presentations. Genetic diagnoses were made in all CHD classes. Diagnostic yield was higher in syndromic appearing infants, but geneticists’ dysmorphology exams lacked complete sensitivity and 6.5% of isolated CHD cases had diagnostic CMA. Interestingly, diagnostic results (15.8%) in left ventricular outflow tract obstruction (LVOTO) defects occurred most often in patients with isolated CHD. Geneticists’ evaluations were particularly important for second-tier molecular testing (10.5% test-specific yield), bringing the overall genetic testing yield to 17%. We assess these results in the context of previous studies. Cumulative evidence provides a rationale for comprehensive, standardized genetic evaluation in infants with severe CHDs regardless of lesion or extracardiac anomalies because genetic diagnoses that impact care are easily missed. These findings support routine CMA testing in infants with severe CHDs and underscore the importance of copy-number analysis with newer testing strategies such as exome and genome sequencing. |
| first_indexed | 2024-03-10T08:47:52Z |
| format | Article |
| id | doaj.art-882703b5dfcb4f94ba771a46c94f8a24 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T08:47:52Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-882703b5dfcb4f94ba771a46c94f8a242023-11-22T07:46:36ZengMDPI AGGenes2073-44252021-08-01128124410.3390/genes12081244Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the LiteratureBenjamin M. Helm0Benjamin J. Landis1Stephanie M. Ware2Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USAThe use of clinical genetics evaluations and testing for infants with congenital heart defects (CHDs) is subject to practice variation. This single-institution cross-sectional study of all inpatient infants with severe CHDs evaluated 440 patients using a cardiovascular genetics service (2014–2019). In total, 376 (85.5%) had chromosome microarray (CMA), of which 55 (14.6%) were diagnostic in syndromic (N = 35) or isolated (N = 20) presentations. Genetic diagnoses were made in all CHD classes. Diagnostic yield was higher in syndromic appearing infants, but geneticists’ dysmorphology exams lacked complete sensitivity and 6.5% of isolated CHD cases had diagnostic CMA. Interestingly, diagnostic results (15.8%) in left ventricular outflow tract obstruction (LVOTO) defects occurred most often in patients with isolated CHD. Geneticists’ evaluations were particularly important for second-tier molecular testing (10.5% test-specific yield), bringing the overall genetic testing yield to 17%. We assess these results in the context of previous studies. Cumulative evidence provides a rationale for comprehensive, standardized genetic evaluation in infants with severe CHDs regardless of lesion or extracardiac anomalies because genetic diagnoses that impact care are easily missed. These findings support routine CMA testing in infants with severe CHDs and underscore the importance of copy-number analysis with newer testing strategies such as exome and genome sequencing.https://www.mdpi.com/2073-4425/12/8/1244congenital heart diseasechromosome microarray analysisgenetic testingmutationdysmorphiccardiac classification |
| spellingShingle | Benjamin M. Helm Benjamin J. Landis Stephanie M. Ware Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the Literature Genes congenital heart disease chromosome microarray analysis genetic testing mutation dysmorphic cardiac classification |
| title | Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the Literature |
| title_full | Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the Literature |
| title_fullStr | Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the Literature |
| title_full_unstemmed | Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the Literature |
| title_short | Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the Literature |
| title_sort | genetic evaluation of inpatient neonatal and infantile congenital heart defects new findings and review of the literature |
| topic | congenital heart disease chromosome microarray analysis genetic testing mutation dysmorphic cardiac classification |
| url | https://www.mdpi.com/2073-4425/12/8/1244 |
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