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Cowden Syndrome and Bannayan-Riley-Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: a clinical study of 42 individuals with PTEN mutations
  1. Katherine L Lachlan (katherine.lachlan{at}
  1. Wessex Clinical Genetics Service and Division of Human Genetics, Southampton University, United Kingdom
    1. Anneke M Lucassen (a.m.lucassen{at}
    1. Wessex Clinical Genetics Service and Division of Cancer Sciences, Southampton University, United Kingdom
      1. David J Bunyan (dave.bunyan{at}
      1. Wessex Regional Genetics Laboratory, United Kingdom
        1. I Karen Temple (ikt{at}
        1. Wessex Clinical Genetics Service and Devision of Human Genetics, Southampton University, United Kingdom


          Background: The most commonly reported phenotypes described in patients with PTEN mutations are Bannayan Riley Ruvalcaba syndrome (BRRS), with childhood onset, macrocephaly, lipomas and developmental delay, and Cowden Syndrome (CS); an adult onset condition recognised by mucocutaneous signs, with a risk of cancers in particular of the thyroid and breast. It has been suggested that BRRS and CS are the same condition, but the literature continues to separate them and seek a genotype-phenotype correlation.

          Objective: To study the clinical features of patients with known PTEN mutations and observe any genotype-phenotype correlation.

          Methods: 42 individuals (25 probands and 17 non-probands) from 26 families of all ages with PTEN mutations were recruited through UK Clinical Genetics Services. A full clinical history and examination were undertaken.

          Results: We were unable to demonstrate a genotype-phenotype correlation. Furthermore, by reporting a 31-year-old female with Cowden Syndrome and an exon1 deletion, we were able to refute previous reports that whole exon deletions are only found in patients with a BRRS phenotype.

          Conclusion: Careful phenotyping gives further support for the suggestion that BRRS and Cowden disease are actually one condition, presenting variably at different ages, as in other tumour suppressor disorders such as neurofibromatosis type 1. This has important counselling implications, such as advice about cancer surveillance, for children diagnosed with BRRS.

          • Bannayan-Riley-Ruvalcaba syndrome
          • Cowden Syndrome
          • Genotype-phenotype correlation
          • PTEN
          • variable expressivity

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