22q11.2 deletion syndrome and congenital heart disease

Abstract

The 22q11.2 deletion syndrome has an estimated prevalence of 1 in 4–6,000 livebirths. The phenotype varies widely; the most common features include: facial dysmorphia, hypocalcemia, palate and speech disorders, feeding and gastrointestinal disorders, immunodeficiency, recurrent infections, neurodevelopmental and psychiatric disorders, and congenital heart disease. Approximately 60–80% of patients have a cardiac malformation most commonly including a subset of conotruncal defects (tetralogy of Fallot, truncus arteriosus, interrupted aortic arch type B), conoventricular and/or atrial septal defects, and aortic arch anomalies. Cardiac patients with a 22q11.2 deletion do not generally experience higher mortality upon surgical intervention but suffer more peri‐operative complications than their non‐syndromic counterparts. New guidelines suggest screening for a 22q11.2 deletion in the patient with tetralogy of Fallot, truncus arteriosus, interrupted aortic arch type B, conoventricular septal defects as well as those with an isolated aortic arch anomaly. Early identification of a 22q11.2 deletion in the neonate or infant when other syndromic features may not be apparent allows for timely parental screening for reproductive counseling and anticipatory evaluation of cardiac and noncardiac features. Screening the at‐risk child or adult allows for important age‐specific clinical, neurodevelopmental, psychiatric, and reproductive issues to be addressed.

Clinical Features to Predict 22q11.2 Deletion Syndrome Proven by Molecular Genetic Testing

“…However, the incidence of certain types of cardiac disease is yet unknown as it depends on types of conotruncal defects found, which vary from <1% with DORV to 89% with interrupted aortic arch type B. 24 TOF and pulmonary atresia were the most common types of conotruncal anomalies in our study, similar to prior studies. 27,28 All of our 22q11.2 DS patients were negative for DORV which confirmed the findings reported in the study by Goldmuntz.…”

Consequences of 22q11.2 Microdeletion on the Genome, Individual and Population Levels

“…The penetrance of 22q11.2 microdeletion is high, meaning that almost all individuals with the deletion will have some of symptoms. Clinical presentations of 22q11.2DS can be associated the dysfunction of many organs such as, among others: the heart, palate, brain, immune systems, and endocrine, genitourinary, gastrointestinal systems [ 17 , 18 , 19 , 20 , 21 , 22 ]. Clinical symptoms are so varied that, in the absence of typical craniofacial traits and other common birth defects, such as those of the heart or palate, a diagnosis may be difficult to make.…”

Systemic Screening for 22q11.2 Copy Number Variations in Hungarian Pediatric and Adult Patients With Congenital Heart Diseases Identified Rare Pathogenic Patterns in the Region

“…For tetralogy of Fallot, the proportion of pathogenic CNVs was significantly higher, 17% in our cohort, which is in agreement with the fact that 22q11.2 CNVs are common in conotruncal heart defects ( McDonald-McGinn et al, 1993-2020 ). 22q11.2 deletion can be detected in approximately 20% of all conotruncal heart defects ( Wozniak et al, 2010 ), within this category its prevalence can be as high as ∼50% in interrupted aortic arch type B, ∼35% in truncus arteriosus or 10–25% in tetralogy of Fallot ( Goldmuntz, 2020 ). All these suggest an absolute indication for 22q11.2 CNV analysis in these CHD groups, especially when co-occurring with at least one extracardiac manifestation or dysmorphic traits ( Wozniak et al, 2010 ).…”

“…Clinical diagnosis may be challenging and significantly delayed due to the large phenotypic spectrum resulting from 22q11.2 CNVs (from asymptomatic appearance to multiple defects) ( van Engelen et al, 2010 ). Previous studies have drawn attention to the importance of routine screening for 22q11.2 CNVs in patients with congenital heart defects, especially with conotruncal anomalies ( Wozniak et al, 2010 ; Huber et al, 2014 ; Goldmuntz, 2020 ).…”