Constitutional Mutation of PIK3CA: A Variant of Cowden Syndrome?

We present a family in which four individuals have been identified with the same likely pathogenic genetic alteration in the <i>PIK3CA</i> 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 <i>PIK3CA</i> 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 <i>PIK3CA</i>, which may be shared with other hereditary breast and ovarian cancer syndromes.