Genetic heterogeneity and phenotypic anomalies in children with atrioventricular canal defect and tetralogy of Fallot

Abstract

Tetralogy of Fallot associated with the atrioventricular canal defect has been usually reported in association with Down syndrome. The aim of the present study was to describe the cardiac aspects and the genetic anomalies in children with this association of heart defects. We identified 64 patients with atrioventricular canal defect tetralogy of Fallot. All children underwent complete cardiovascular, clinical phenotypic and genetic evaluation. A genetic syndrome or extracardiac anomalies were found in 56 patients (87.5%). Down syndrome (43 patients, 67.2%) was the most frequent genetic diagnosis. Other syndromes were 8p deletion, trisomy 13, duplication 5p, cranio-cerebello-cardiac syndrome, Cantrell syndrome, CHARGE association, VACTERL association, and DiGeorge syndrome related to maternal diabetes. No patients in our series had 22q11 deletion. Tetralogy of Fallot with extreme dextroposition of the aorta was found in seven patients (only one with Down syndrome). Additional cardiac malformations were present in 23 patients (only 11 with Down syndrome). The association between atrioventricular canal defect and tetralogy of Fallot represents a cardiac phenotype with strong genetic characteristics. For this reason, a careful genetic examination is required. Our study confirms the high prevalence of Down syndrome, but also reveals a significant genetic heterogeneity. Additional cardiac defects are prevalent in patients without Down syndrome.

Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot

“…In our study patients with Down syndrome did not present coarctation of the PA, MAPCAs or coronary artery abnormalities. Furthermore, our study confirmed that pronounced dextroposition of the aorta is very rare in patients with Down syndrome 56. Our finding of a single patient with Down syndrome and SAA is in line with previous data showing SAA in one out of 43 patients 56.…”

“…Furthermore, our study confirmed that pronounced dextroposition of the aorta is very rare in patients with Down syndrome 56. Our finding of a single patient with Down syndrome and SAA is in line with previous data showing SAA in one out of 43 patients 56. Thus, ToF in Down syndrome seems to be associated with a relatively uniform cardiac phenotype.…”

“…Our study confirmed previous results that about 25% of patients with ToF and Down syndrome have AVSD, and in children with ToF and associated AVSD the presence of genetic syndromes, mostly Down syndrome, is very high (>85%) 56. In our study patients with Down syndrome did not present coarctation of the PA, MAPCAs or coronary artery abnormalities.…”

Double outlet right ventricle: aetiologies and associations

“…Prenatal exposures to ethanol, retinoic acid or theophylline with adrenergic agonists have been reported in humans with DORV 61 62. Of note, similar teratogens have been associated with TOF63 – 65 and may influence pathways unique to type I DORV.…”

Cardiopatia Congénita em Crianças com Síndrome de Down: O que Mudou nas Últimas Três Décadas?

“…Esta cardiopatia, de difícil abordagem cirúrgica, apresenta uma associação conhecida com o SD 16 e provavelmente uma embriogénese particular nesta síndrome, uma vez que as duas cardiopatias apresentam origens embriogénicas muito distintas. [16][17] Nove por cento dos doentes da nossa amostra (9/102) foram submetidos a cirurgia paliativa. Destes, quatro corresponderam a shunts sistémico-pulmonares no contexto de ToF e em cinco casos foi realizado banding da artéria pulmonar em doentes com DCSAV, por apresentarem ventrículos desproporcionados, muito baixo peso, outras patologias não cardíacas associadas, com aumento do risco cirúrgico, ou HAP grave.…”