%0 Journal Article
%T Severe coarctation of the aorta, developmental delay, and multiple dysmorphic features in a child with SMAD6 and SMARCA4 variants.
%A Caengprasath N
%A Buasong A
%A Ittiwut C
%A Khongphatthanayothin A
%A Porntaveetus T
%A Shotelersuk V
%J Eur J Med Genet
%V 65
%N 11
%D Nov 2022
%M 36049609
%F 2.465
%R 10.1016/j.ejmg.2022.104601
%X Pathogenic variants in SMARCA4 cause Coffin-Siris syndrome (CSS) while those in SMAD6 lead to aortic valve disease and other dysmorphisms. We identified a 6-year-old Thai boy with features of CSS alongside unusual manifestations including, very severe coarctation of the aorta (CoA) requiring coarctectomy in the neonatal period and bilateral radioulnar synostoses. Trio exome sequencing revealed that the patient harbored two de novo variants, a missense c.2475G > T, p.(Trp825Cys) in SMARCA4 and a nonsense c.652C > T, p.(Gln218Ter) in SMAD6. Both of which have never been previously reported. The clinical presentations in our patient are a result of the combinational features of each genetic variant: the SMARCA4 p.(Trp825Cys) variant leads to facial features of Coffin Siris syndrome and Dandy-Walker malformation, while the SMAD6 p.(Gln218Ter) variant underlies radioulnar synostosis. Interestingly, the severity of CoA in the proband is beyond the phenotypic spectra of each genetic variant and may be a result of the synergistic effects of both variants. Here, we report a child with variants in SMARCA4 or SMAD6 with combined features of each plus a severe CoA, possibly due to an additive effect of each variant.