Variable Intrafamilial Cardiac Phenotype Segregating With a TBX20 Missense Variant in the Putative Transcriptional Activation Domain

Non-syndromic atrioventricular canal (AVC) occurs in ∼1/1000 livebirths and most of them are considered sporadic cases or the result of multifactorial inheritance. We report on a fetus diagnosed with non-syndromic AVC, whose mother showed interatrial septal tissue redundancy and slight ascending aortic ectasia. Trio-based exome sequencing (ES), performed during the pregnancy, detected the maternally inherited rare c.946A > G p.(Thr316Ala) missense variant in the TBX20 gene as the reasonable cause of this condition. Segregation analysis extended to the grandmother, previously diagnosed with isolated ascending aortic ectasia, disclosed the presence of the same variant. This is the first case of AVC familial spectrum caused by a TBX20 variant in the putative transcriptional activation domain. Moreover, this case highlights a possible common molecular cause underlying distinct and not previously associated cardiac conditions.