Mosaic partial deletion of the PTEN gene in a patient with Cowden syndrome

Cowden syndrome is an autosomal dominant condition caused by pathogenic mutations in the phosphatase and tensin homolog (PTEN) gene. Only a small proportion of identified pathogenic mutations have been reported to be large deletions and rearrangements. We report on a female patient with a previous history of breast ductal carcinoma in situ who presented to our institution for management of gastrointestinal hamartomatous polyposis. Although several neoplastic predisposition syndromes were considered, genetic evaluation determined that the patient met clinical diagnostic criteria for Cowden syndrome. Array-based comparative genomic hybridization was performed and revealed a mosaic partial deletion of the PTEN gene. Follow-up clinical history including bilateral thyroid nodules, dermatological findings, and a new primary "triple-negative" adenocarcinoma of the contralateral breast are discussed. We highlight the need for recognition and awareness of mosaicism as it may provide an explanation for variable phenotypic presentations and may alter the genetic counseling risk assessment of affected individuals and family members.