# Constitutional Mutation of PIK3CA: A Variant of Cowden Syndrome?

## TL;DR

A family with a PIK3CA mutation shows signs similar to Cowden syndrome, suggesting it may be a variant of the condition.

## Contribution

This report adds to the understanding of PIK3CA mutations in hereditary breast and ovarian cancer syndromes.

## Key findings

- Four family members share a likely pathogenic PIK3CA mutation.
- Clinical features include thyroid and ovarian abnormalities.
- PIK3CA should be considered in Cowden-like cases without other mutations.

## Abstract

We present a family in which four individuals have been identified with the same likely pathogenic genetic alteration in the PIK3CA gene at the germinal level; specifically, c.1145G>A p.(Arg382Lys) missense type. The index case patient was diagnosed with multinodular goiter and breast cancer at 61 years old. Among the other three carrier relatives: one has been diagnosed with serous cystadenoma of the ovary and a thyroid nodule with no radiological suspicion of malignancy; the other two present multinodular goiter. Additionally, a sister of three of the carriers suffered from an ovarian teratoma, follicular thyroid carcinoma on multinodular goiter, and high-grade serous ovarian carcinoma. No direct mutation study was performed on her as she had died due to ovarian carcinoma. This finding suggests that the PIK3CA gene should be considered in Cowden-like families when no other gene mutations have been found. Furthermore, this report contributes to characterization of the clinical phenotype caused by mutations in PIK3CA, which may be shared with other hereditary breast and ovarian cancer syndromes.