SMAD4 mutation and the combined syndrome of juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia.

Juvenile polyposis syndrome (JPS) and hereditary haemorrhagic telangiectasia (HHT) are autosomal dominant disorders with characteristic clinical phenotypes. Recently, reports of the combined syndrome of JPS and HHT have been described in individuals with mutations in the SMAD4 gene, whose product-SMAD4-is a critical intracellular effector in the signalling pathway of transforming growth factor beta (TGFbeta). This report describes a 24-year-old man who presented to the Respiratory Institute after colectomy for JPS with a SMAD4 mutation and who was subsequently diagnosed to have HHT with asymptomatic cerebral and pulmonary arteriovenous malformations (AVMs). Patients with JPS due to a SMAD4 mutation should be screened for the vascular lesions associated with HHT, especially occult AVMs in visceral organs, which may potentially present catastrophically with serious medical consequences.