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

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.

pten phosphohydrolase, report, mutation, human, thyroid, lipoma, child, terminology as topic, phenotype, genetics, physiology, expression, aged, childhood, patients, literature, female, humans, male, syndrome, preschool, hospitals, research, methods, classification, risk, genetic heterogeneity, hamartoma syndrome, protein, research support, age factors, adolescent, family, exons, genotype, adult, history, penetrance, middle aged, multiple, cancer

10.1136/jmg.2007.049981

0022-2593

579-585

Lachlan, K.L.

175ce889-ede8-477e-93eb-afefc1af5dda

Lucassen, A.M.

2eb85efc-c6e8-4c3f-b963-0290f6c038a5

Bunyan, D.

53a89b0f-cfde-4f58-87f3-084c8e9c774e

Temple, I.K.

d63e7c66-9fb0-46c8-855d-ee2607e6c226

2007

Lachlan, K.L.

175ce889-ede8-477e-93eb-afefc1af5dda

Lucassen, A.M.

2eb85efc-c6e8-4c3f-b963-0290f6c038a5

Bunyan, D.

53a89b0f-cfde-4f58-87f3-084c8e9c774e

Temple, I.K.

d63e7c66-9fb0-46c8-855d-ee2607e6c226

Lachlan, K.L., Lucassen, A.M., Bunyan, D. and Temple, I.K. (2007) 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. Journal of Medical Genetics, 44 (9), 579-585. (doi:10.1136/jmg.2007.049981).

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Published date: 2007

Keywords: pten phosphohydrolase, report, mutation, human, thyroid, lipoma, child, terminology as topic, phenotype, genetics, physiology, expression, aged, childhood, patients, literature, female, humans, male, syndrome, preschool, hospitals, research, methods, classification, risk, genetic heterogeneity, hamartoma syndrome, protein, research support, age factors, adolescent, family, exons, genotype, adult, history, penetrance, middle aged, multiple, cancer