Variety of prenatally diagnosed congenital heart disease in 22q11.2 deletion syndrome

Abstract

ObjectiveTo analyze the spectrum of prenatally diagnosed congenital heart disease in a Korean population with 22q11.2 deletion syndrome, and to provide guidelines for screening 22q11.2 deletion prenatally.MethodsThis retrospective study evaluated 1,137 consecutive fetuses that had prenatal genetic testing for 22q11.2 deletion because of suspected congenital heart disease between September 2002 and December 2012, at Asan Medical Center, Seoul, Korea.ResultsMain cardiovascular diseases in the 53 fetuses with confirmed 22q11.2 deletions were tetralogy of Fallot (n = 24, 45%), interrupted aortic arch (n = 10, 19%), ventricular septal defect (n = 5, 9%), double outlet right ventricle (n = 4, 8%), and coarctation of the aorta (n = 4, 8%). Other cardiac defects were rarely associated with 22q11.2 deletion. One fetus had persistent truncus arteriosus, one had aortic stenosis, and one had hypoplastic right heart syndrome. Two fetuses had normal intracardiac anatomy with an isolated right aortic arch, and one had an isolated bilateral superior vena cava.ConclusionA variety of congenital heart diseases were seen during the prenatal period. Conotruncal cardiac defects except transposition of great arteries were strongly associated with 22q11.2 deletion. When such anomalies are diagnosed by fetal echocardiography, genetic testing for 22q11.2 deletion should be offered. Even if less frequent deletion-related cardiac defects are detected, other related anomalies, such as thymic hypoplasia or aplasia, should be evaluated to rule out a 22q11.2 deletion.

Congenital heart diseases and cardiovascular abnormalities in 22q11.2 deletion syndrome: From well‐established knowledge to new frontiers

“…Moreover, Noel reported 2 fetuses with HLHS (3% of all CHDs) (Noel et al, 2014). These data suggest that the prevalence of CHDs, especially that of the most severe CHDs, may be even higher in 22q11.2DS but they may also reflect a bias of ascertainment of those patients noted on ultrasound to have CHD (Bretelle et al, 2010; Lee et al, 2014; J. Zhang et al, 2015).…”

“…AAA, either in association with intracardiac anomalies or isolated, are also commonly seen: cervical aortic arch (CAA), double aortic arch (DAA), right-sided aortic arch (RAA), and abnormal origin of the subclavian arteries (Kazuma, Murakami, Suzuki, Umezu, & Murata, 1997; Momma, Matsuoka, & Takao, 1999; McElhinney et al, 2001). Less often, other cardiovascular anomalies have been reported in patients with 22q11.2DS including, hypoplastic left heart syndrome (HLHS), transposition of great arteries, double outlet right ventricle, total anomalous pulmonary venous connection, atrial septal defect, tricuspid atresia, pulmonary valve stenosis, bicuspid aortic valve or aortic valve stenosis, aortic origin of a pulmonary artery (PA) (hemitruncus arteriosus), crossing PAs or malposition of the branch PAs (Babaoğlu et al, 2013; Consevage et al, 1996; Lee et al, 2014; Marble, Morava, Lopez, Pierce, & Pierce, 1998; Marino, Digilio, Giannotti, & Dallapiccola, 1996; Marino, Digilio, Novelli, Giannotti, & Dallapiccola, 1997; McDonald-McGinn et al, 2001; Melchionda et al, 1995; Momma, 2010; Recto, Parness, Gelb, Lopez, & Lai, 1997; J. Zhang et al, 2015).…”

Congenital Aortic Stenosis in a Fetus: A Case Report and Review of Syndromic Associations

“…Ejection fraction increased by 7% with a 20 ml/msq decrease in left ventricular end diastolic volume, compared to a worsening of both parameters with standard treatment alone. In addition, the inflammatory process assessed by plasma C reactive protein concentration, progressed in patients on standard treatment but remained stable in those receiving trimetazidine [15]. These benefits have been confirmed in 200 patients with multi-vessel coronary artery disease and left ventricular dysfunction.…”

“…However, in view of possibility of gonadal mosaicism for the deletion in one of the parent, prenatal diagnosis is recommended in a couple who have a child with Williams syndrome [9]. Figure 2a shows the facial gestalt of two children with Williams syndrome [14,15]. Figure 2d shows facial gestalt of Di George syndrome.…”

Integrated Sequence Assembly-based Approach for Calling Genomic Long Insertion

“…Even though de novo assembly potentially can identify insertions of any size, the high computational cost and memory requirements have made it difficult to use in practice. For these reasons we developed ISALins, many studies have shown that genetic structural variants are associated with human performance, including cancer, mental disorders, metabolic disorders, and a variety of incurable diseases, such as the heterozygous variant of gene NRXN1 associated with autism and schizophrenia; Congenital heart defects is closely related to the lack of 22q11.2 area [9]. Second-generation sequencing technology is an important step forward in our understanding of the human genetic structure and explains the relationship between genetic variation and disease.…”