SMAD4 and Myhre syndrome: For example, a 14-year-old girl with short stature, neurodevelopmental disability, and cardiac valvular disease who had not had prior exome testing had a de novo missense variant by FGA, occurring on the paternal allele in SMAD4, NM_005359:c.1498A>G, p.Ile500Val (Fig. 4b), diagnostic of Myhre syndrome (OMIM #139210), which is associated with increased risk of pericardial, pulmonary, and tracheal fibrosis, as well as skeletal and vascular complications.