Genital lentigines in a 6-year-old boy with a family history of Cowden's disease: clinical genetic evidence of the linkage between Baanyan-Riley-Ruvacalba syndrome and Cowden's disease

Background: In 1997, it was reported that a PTEN gene deletion, a common genetic mutation in Cowden's disease (CD), was identified in a patient with Bannayan-Riley-Ruvacalba (BRR), suggesting that the two diseases were allelic. However, the clinical overlap between die two diseases has largely remained unclear. Objective: To confirm the genetic and clinical association in a family segregating both CD and BRR. Methods: Clinical evaluation and genetic analysis using a denaturing gradient gel electrophoresis (DGGE), temporal temperature gradient electrophoresis (TTGE), and DNA sequencing techniques. Results: Our patient presents with typical BRR clinical manifestations, including multiple lentigines on his penis, while his mother presents with typical manifestations of CD, including multiple malignancies. Genetic analyses of leukocytes from the patient and his mother showed mutations in exon 8 that was identified as die presumably truncating mutation R335X. Conclusion: This report provides clinical evidence that both BRR and CD are closely related and confirms the PTEN gene mutation in BRR and CD patients segregating in die same family, thus confirming the genetic linkage between the two genodermatoses.