Genetics and Genetic Testing in Congenital Heart Disease

Cowan, Jason; Ware, Stephanie M.

doi:10.1016/j.clp.2015.02.009

Cited by 118 publications

(137 citation statements)

References 96 publications

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“…Early diagnosis of a genetic syndrome allows for genetic counseling and early implementation of comprehensive care and recommended health supervision. Some have argued that genetic screening in CHD should be more rigorous [36, 37], but this practice has not uniformly been adapted and screening rates continue to be low [38–40]. Genetic screening practices continue to evolve, providing a growing body of information to clinicians and patients and the issue of who to screen and what to do with the information will become more pressing.…”

Section: Commentmentioning

confidence: 99%

Prevalence of Noncardiac and Genetic Abnormalities in Neonates Undergoing Cardiac Operations: Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database

Patel

Costello

Backer

et al. 2016

The Annals of Thoracic Surgery

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Background Among congenital heart disease (CHD) patients, the coexistence of non-cardiac congenital anatomic abnormalities (NC), genetic abnormalities (GA), and syndromes (S) may influence therapeutic strategies and outcomes. The appreciated prevalence of these abnormalities has risen, as increased screening and improved diagnostic precision enable identification of these comorbidities in a larger fraction of neonates with CHD. We examined the contemporary prevalence and distribution of NC/GA/S across diagnostic groups among neonates undergoing cardiac surgery using a large, nationally representative clinical registry. Methods The Society of Thoracic Surgeons-Congenital Heart Surgery Database (STS-CHSD) was queried to identify neonates (≤ 30 days) who underwent index cardiac operations from 2010–2013. The fundamental cardiac diagnosis was used to identify 10 diagnostic groups. The prevalence of NC/GA/S was reported across each group. Results The cohort included 15,376 index neonatal operations from 112 centers. Overall 18.8% (2,894/15,376) of operations were performed on neonates with NC/GA/S. Patients with atrioventricular septal defect (212/357, 59.4%), interrupted aortic arch (248/567, 43.7%), truncus arteriosus (204/554, 36.8%), tetralogy of Fallot (417/1383, 30.2%) had the highest prevalence of NC/GA/S abnormalities, whereas those with transposition (111/2778, 4.0%) had the lowest prevalence. The most commonly identified NC/GA/S included: heterotaxy (597/15,376, 3.9%), DiGeorge/22q11 deletion (550/15,376, 3.6%), Down syndrome/trisomy 21 (318/15, 376, 2.1%), intestinal malrotation (220/15,376, 1.4%), and Turner syndrome/45XO (189/15,376, 1.2%). Conclusions The prevalence of NC/GA/S varies widely across CHD diagnostic groups. This information may be useful for patient counseling, recommendations for screening for anomalies and genetic disorders, and perioperative management.

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Section: Commentmentioning

confidence: 99%

Prevalence of Noncardiac and Genetic Abnormalities in Neonates Undergoing Cardiac Operations: Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database

Patel

Costello

Backer

et al. 2016

The Annals of Thoracic Surgery

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“…CNVs are known to be important causes of CHD: about 10% are due to numerical chromosomal abnormalities and 15% to submicroscopic changes, occurring in approximately 3-25% of the syndromic cases and 3-10% of nonsyndromic cases [Kerstjens-Frederikse and Hofstra, 2013;Cowan and Ware, 2015]. Monogenic mutations are reported in 5 and 10% of syndromic and nonsyndromic cases, respectively [Kerstjens-Frederikse and Hofstra, 2013;Cowan and Ware, 2015], but this number will probably increase with the use of next-generation sequencing (NGS) for large-scale diagnosis [Landis and Ware, 2016].…”

Section: Major Contribution Of Genomic Copy Number Variation In Syndrmentioning

confidence: 99%

“…Monogenic mutations are reported in 5 and 10% of syndromic and nonsyndromic cases, respectively [Kerstjens-Frederikse and Hofstra, 2013;Cowan and Ware, 2015], but this number will probably increase with the use of next-generation sequencing (NGS) for large-scale diagnosis [Landis and Ware, 2016]. Using standard cytogenetic techniques, only a subset of these patients are diagnosed because of the limited cytogenetic resolution, which is incapable of detecting changes smaller than 5-10 Mb [Richards and Garg, 2010].…”

Section: Major Contribution Of Genomic Copy Number Variation In Syndrmentioning

confidence: 99%

Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test

et al. 2017

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Congenital heart disease (CHD) is the most common congenital disorder among live births. When associated with extracardiac abnormalities, it is characterized as a syndromic heart disease (syndromic CHD) and corresponds to 25% of all liveborn infants with a heart defect. The etiology in about 65% of the cases still remains unknown, and in about 35% of the patients, it is associated with genetic factors. In the present study, MLPA and SNP-array techniques were used to investigate a group of 47 patients with syndromic CHD. In total, 16 defects (34%) were identified, of which 12 (25.5%) were classified as pathogenic or probably pathogenic. The most frequent abnormalities were 22q11.2 deletion (22q11.2 deletion syndrome) and 7q11.23 deletion (Williams-Beuren syndrome). We also show that rarer malformations may be associated with syndromic CHD, such as 14q32.33 deletion as well as 17q25.3, 15q11.2 (BP1-BP2), 22q13.31, and 12p13.31 (SLC2A3) duplications. The present study demonstrates that CNVs are important causal factors and should be studied in patients with syndromic CHD. Furthermore, the use of MLPA as a first screening test was appropriate, as this less expensive technology detected 11 of the 12 pathogenic abnormalities (91.6%).

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“…Recurrence risk for LVOTO defects in first-degree family members can be stratified by taking lesion and relation to the affected family member into consideration (Cowan and Ware 2015). Confirmation of syndromic vs. non-syndromic disease can also help to refine recurrence risk.…”

Section: Genetic Counseling and Family Screening Recommendationsmentioning

confidence: 99%

“…A more recent study found a recurrence risk in the siblings of BAV probands to be 10.1 % (Hales and Mahle 2014). Cowan and Ware (2015) include a list of recurrence risk for various CHDs, including known data for LVOTO defects (Cowan and Ware 2015). However, specific recurrence risk data may not be available for some lesions.…”

Section: Genetic Counseling and Family Screening Recommendationsmentioning

confidence: 99%

Bicuspid Aortic Valve: a Review with Recommendations for Genetic Counseling

Freeze

Landis

Ware

et al. 2016

Journal of Genetic Counseling

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Bicuspid aortic valve (BAV) is the most common congenital heart defect and falls in the spectrum of left-sided heart defects, also known as left ventricular outflow tract obstructive (LVOTO) defects. BAV is often identified in otherwise healthy, asymptomatic individuals, but it is associated with serious long term health risks including progressive aortic valve disease (stenosis or regurgitation) and thoracic aortic aneurysm and dissection. BAV and other LVOTO defects have high heritability. Although recommendations for cardiac screening of BAV in at-risk relatives exist, there are no standard guidelines for providing genetic counseling to patients and families with BAV. This review describes current knowledge of BAV and associated aortopathy and provides guidance to genetic counselors involved in the care of patients and families with these malformations. The heritability of BAV and recommendations for screening are highlighted. While this review focuses specifically on BAV, the principles are applicable to counseling needs for other LVOTO defects.

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Genetics and Genetic Testing in Congenital Heart Disease

Cited by 118 publications

References 96 publications

Prevalence of Noncardiac and Genetic Abnormalities in Neonates Undergoing Cardiac Operations: Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database

Prevalence of Noncardiac and Genetic Abnormalities in Neonates Undergoing Cardiac Operations: Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database

Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test

Bicuspid Aortic Valve: a Review with Recommendations for Genetic Counseling

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