Cowden and Cowden-Like Syndrome: Tales from the Other Strand

Inactivation of the tumor-suppressor gene PTEN is well-established as the cause of Cowden syndrome (CS), characterized by macrocephaly; mucocutaneous findings of trichilemmomas, keratoses, and papules; and predisposition to thyroid and breast cancers. PTEN normally damps signaling pathways that promote cell survival and proliferation. In 80% of autosomal dominant CS, affected individuals inherit an inactive mutant allele of PTEN. The other, normal copy is subsequently inactivated in the tumors that develop. The presentation of Cowden syndrome is strikingly diverse; some patients exhibit characteristic features without meeting diagnostic criteria for CS. Cowden-like syndrome (CLS) is the diagnosis in these patients, few of whom have mutation…