SMAD4 and Global developmental delay: Inactivated SMAD4 mutation causes Myhre syndrome, which is a developmental disorder characterized by short stature, short hands and feet, facial dysmorphism, muscular hypertrophy, deafness, and cognitive delay.117,118 Myhre syndrome patients carry an I500 mutation at Smad4 that results in a stabilized but unfunctional mutant.118,241