Autosomal dominant- germline mutation in PTEN gene (tumor suppressor) on 10q.
Manifests as hamartomatous GI polyps, lipomas, fibromas, GU malformations, and multiple cutaneous lesions (facial tricholemmomas, papillomas, palmoplantar keratosis, palmoplantar hyperkeratotic pits). Microcephaly and mental retardation are common.
Increased risk of malignancy of the breast, thyroid (follicular ca), colon and endometrium
Proteus syndrome also associated with PTEN mutations- variable manifestations, mosaic distribution- connective tissue nevi, assymmetric limb growth, skull hyperostosis, megaspondylodysplasia of vertebrae, visceral overgrowth (spleen and thymus particularly)