ORIGINAL ARTICLE

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

K L Lachlan^1,2, A M Lucassen^1,3, D Bunyan⁴, I K Temple^1,2

¹ Wessex Clinical Genetics Service, Southampton University Hospitals Trust, Southampton, UK
² Division of Human Genetics, Southampton Medical School, University of Southampton, Southampton, UK
³ Division of Cancer Sciences, Southampton Medical School, University of Southampton, Southampton, UK
⁴ Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK

Correspondence to:
Dr Katherine Lachlan
Wessex Clinical Genetics Service, Princess Anne Hospital, Coxford Road, Southampton, SO16 5YA, UK; katherine.lachlan{at}suht.swest.nhs.uk

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.

Conclusion: 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.

Abbreviations: BRRS, Bannayan–Riley–Ruvalcaba syndrome; CS, Cowden syndrome; VATER, vertebral defects, anal atresia, trachea-oesophageal fistula with oesophageal atresia, radial and renal abnormalities

Keywords: PTEN; Bannayan-Riley-Ruvalcaba syndrome; Cowden Syndrome; genotype-phenotype correlation; variable expressivity

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