As such, this might explain the marked clinical variability of SMAD6-deficient patient with BAV-related aortopathy as predominant phenotype, and, emphasises the complexity of CHD, in which gene dosage, timing, haemodynamic flow, and its interplay with other signalling pathways like Notch and TGF-β are important too. Here, SMAD6 is linked to coronary artery disorder.