While mutations in SMAD4 cause only a small percentage (∼2%) of all HHT (Gallione et al., 2006; Lesca et al., 2006; Prigoda et al., 2006), the medical management considerations for the resulting JP/HHT Syndrome are such that ruling out a mutation in this gene is clinically relevant. The gene discussed is SMAD4; the disease is hereditary hemorrhagic telangiectasia.