Genetics of PTEN Hamartoma Tumour Syndrome


The PTEN hamartoma tumour syndrome (PHTS) represents a group of clinically related syndromes caused by germline mutations in the PTEN gene. These include Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome, adult Lhermitte–Duclos disease and autism spectrum disorders with macrocephaly. PTEN mutations lead to increased cancer risks (including breast, thyroid, uterine, renal cell and colon cancers) and benign overgrowth of multiple tissues, presenting in part as dermatologic lesions, gastrointestinal polyps, thyroid structural lesions, lipomas and vascular lesions. Historically, data on the clinical features of PHTS have been based primarily on collected case reports from the literature. More recently, findings from several large United States and European cohorts have added greatly to our understanding of PHTS. The bulk of these data are on patients with CS, the most common of the PHTS component syndromes. Testing and management criteria and recently revised clinical diagnostic criteria have been established for PHTS.

Key Concepts:

  • PHTS is an important group of clinical disorders, including Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome, which are defined by presence of a mutation in the PTEN gene.

  • These conditions are of relevance to many clinical specialties because of significantly increased risks for benign and malignant tissue overgrowth.

  • The data that are available on risks for malignancy and other features of the syndrome have been almost entirely obtained on cohorts of patients who presented to medical attention and were tested because they demonstrated a significant number of PHTS features. This inherently should lead to overestimates of the prevalence of these features.

  • Projected lifetime cancer risks in recent studies have been approximately 77–85% for breast cancer (women only), 20–38% for thyroid cancer, 20–30% for uterine cancer, 15–34% for renal cell carcinoma and 9–16% for colon cancer.

  • Common nonmalignant features include gastrointestinal polyps, macrocephaly, specific skin lesions and structural thyroid lesions. Less common features include Lhermitte–Duclos disease, autism spectrum disorder, mental retardation/developmental delay, testicular lipomatosis and vascular anomalies.

  • Criteria for making a clinical diagnosis of this syndrome have been recently updated to reflect current literature.

  • The US National Comprehensive Cancer Network has developed testing criteria and medical management criteria which are updated annually.

Keywords: PTEN; PTEN hamartoma tumour syndrome; Cowden syndrome; Bannayan–Riley–Ruvalcaba syndrome


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Further Reading

Hollander MC, Blumenthal GM and Dennis PA (2011) PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nature Reviews Cancer 11(4) :289–301.

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Pilarski, Robert T(Jul 2014) Genetics of PTEN Hamartoma Tumour Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025733]