PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow-up protocol

PTEN hamartoma tumor syndromes (PHTS) are a spectrum of hamartomatous overgrowth syndromes associated with germ-line mutations in the tumor suppressor PTEN gene located on 10q23.3. It is widely accepted that two of these disorders, Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, are allelic conditions. Because PTEN mutations are not identifiable in every case of the PHTS phenotype, the inability to detect a mutation within the PTEN gene does not invalidate the clinical diagnosis of Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, in patients who meet diagnostic criteria for these disorders. PTEN mutations are associated with an increased risk for developing breast, thyroid, endometrial, and sometimes renal cancers. Thus, cancer surveillance is the cornerstone of PHTS patient management. Although a consensus cancer surveillance protocol has not been formally instituted, all PTEN mutation carriers should adopt the cancer surveillance strategies proposed for patients with Cowden syndrome. In addition, because gastrointestinal and vascular complications can be more severe in Bannayan-Riley-Ruvalcaba syndrome than in Cowden syndrome, patients with Bannayan-Riley-Ruvalcaba syndrome should be monitored from this point of view too. In this study, we report on two cases with Bannayan-Riley-Ruvalcaba phenotype that showed two different PTEN mutations. We also propose practice recommendations for management of PHTS patients.