title: Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers.
abstract: 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 those 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
  In total, 42 people (25 probands and 17 non-probands) from 26 families of all ages with PTEN mutations were recruited through the UK clinical genetics services. A full clinical history and examination were undertaken.
  
  
  RESULTS
  We were unable to demonstrate a genotype-phenotype correlation. Furthermore, our findings in a 31-year-old woman with CS and an exon 1 deletion refutes previous reports that whole exon deletions are only found in patients with a BRRS phenotype.
  
  
  CONCLUSIONS
  Careful phenotyping gives further support for the suggestion that BRRS and CS 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.
authors.affiliation: Wessex Clinical Genetics Service, Southampton University Hospitals Trust, Southampton, UK. katherine.lachlan@suht.swest.nhs.uk
authors.forename: K L
authors.initials: KL
authors.lastname: Lachlan
authors.forename: A M
authors.initials: AM
authors.lastname: Lucassen
authors.forename: D
authors.initials: D
authors.lastname: Bunyan
authors.forename: I K
authors.initials: IK
authors.lastname: Temple
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006223:Hamartoma Syndrome, Multiple / Q000145:classification / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000502:physiology; D019683:Penetrance; D010641:Phenotype; D013577:Syndrome; D009626:Terminology as Topic
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human