GJA4 and vascular malformation: We postulate that loss of function of the GJA4 gene produces absence of ductus venosus, a converse effect to gain of function mutation (generation of vascular malformations in skin and liver, and orbit), and fetal nuchal edema due to lymphatic dysfunction. Further research is required to confirm or negate this association. A limitation of this study is the non-availability of functional analysis of this specific variant using RNA or protein studies or cellular or animal modelling.