Abstract
To compare the genetic testing results of neonates with CHD by chromosomal microarray to karyotyping and fluorescence in situ hybridisation analysis. This was a single-centre retrospective comparative study of patients with CHD and available genetic testing results admitted to the cardiac ICU between January, 2004 and December, 2017. Patients from 2004 to 2010 were tested by karyotyping and fluorescence in situ hybridisation analysis, while patients from 2012 to 2017 were analysed by chromosomal microarray. Eight-hundred and forty-nine neonates with CHD underwent genetic testing, 482 by karyotyping and fluorescence in situ hybridization, and 367 by chromosomal microarray. In the karyotyping and fluorescence in situ hybridisation analysis group, 86/482 (17.8%) had genetic abnormalities detected, while in the chromosomal microarray group, 135/367 (36.8%) had genetic abnormalities detected (p < 0.00001). Of patients with abnormal chromosomal microarray results, 41/135 (30.4%) had genetic abnormality associated with neurodevelopmental disorders that were exclusively identified by chromosomal microarray. Conotruncal abnormalities were the most common diagnosis in both groups, with karyotyping and fluorescence in situ hybridisation analysis detecting genetic abnormalities in 26/160 (16.3%) patients and chromosomal microarray detecting abnormalities in 41/135 (30.4%) patients (p = 0.004). In patients with d-transposition of the great arteries, 0/68 (0%) were found to have genetic abnormalities by karyotyping and fluorescence in situ hybridisation compared to 7/54 (13.0%) by chromosomal microarray. Chromosomal microarray identified patients with CHD at genetic risk of neurodevelopmental disorders, allowing earlier intervention with multidisciplinary care and more accurate pre-surgical prognostic counselling.
Highlights
The aetiology of CHD is multifactorial and involves genetics, embryology, and environmental exposures.[1]
Of all patients with abnormal chromosomal microarray analysis results, 76/135 (56.3%) of patients had genetic abnormalities known to be associated with risk for neurodevelopmental disorders
In 46/76 (60.5%) of patients with neurodevelopmental disorders, the genetic abnormality would not have been identified by karyotyping and fluorescence in situ hybridisation analysis testing alone
Summary
The aetiology of CHD is multifactorial and involves genetics, embryology, and environmental exposures.[1] Some forms of CHD are known to have a specific genetic cause[2,3] and most, if not all, patients with moderate-to-severe CHD will undergo some form of genetic testing. As genetic technologies have evolved, so has the detection of genetic variants associated with CHD. The combination was able to diagnose aneuploidies and more subtle genetic abnormalities such as deletions and duplications.[5] Our previous institutional review identified chromosomal abnormalities in 17.8% of neonates with structural heart disease by karyotyping and fluorescence in situ hybridisation analysis.[6] Chromosomal microarray analysis is a valuable clinical tool for the identification of submicroscopic chromosomal aberrations that cannot be detected by conventional cytogenetic methods
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