[MIM 153480], also known as Ruvalcaba-Riley-Smith syndrome, Bannayan-Riley-Ruvalcaba syndrome or Ruvalcaba-Myhre-Smith syndrome, is an autosomal dominant disorder belonging to the family of hamartomatous polyposis syndromes that includes Peutz-Jeghers syndrome (PJS)[MIM 175200], juvenile polyposis (JPS)[MIM 174900) and Cowden disease (CD)[MIM 158350) 1. Hamartomas are benign, hyperplastic, disorganized growths. Characteristic features of BZS include macrocephaly, lipomas, intestinal hamartomatous polyps, vascular malformations, Hashimoto's thyroiditis and speckled penis2-5. In BZS, age at onset is relatively young: many patients present at birth with macrocephaly and failure to thrive5• Malignancies are not hallmarks of BZS. CD is characterized by hamartomas in multiple organs and a risk of breast and thyroid cancer6• While breast tumours occur in 75% of affected females and thyroid disease in 50-75% of CD individuals, macrocephaly (38%) and lipomas (< 5%) are less common, and speckled penis is never observed6• Although the aetiologies of PJS, JPS and CD are known to a greater or lesser extent, the molecular genetic basis of BZS is unknown.