SMAD4 and Myhre syndrome: MYHRS is a rare autosomal-dominant congenital disorder characterized by intellectual disability, dysmorphic facial features, skeletal anomalies, and cardiovascular defects,25 which is caused by heterozygous mutations within either one of two codons (Arg496 and Ile500) of SMAD4. 26SMAD4 is an essential effector of the TGF-β/BMP/activin pathway, acting as a key mediator of signal transduction.27