Head circumference in the clinical detection of PTEN hamartoma tumor syndrome in a clinic population at high-risk of breast cancer

PTEN Hamartoma Tumor Syndrome (PHTS) is often recognized by the presence of macrocephaly and associated mucocutaneous features, and is notable for a profound predisposition to breast and thyroid cancers. Head circumference (HC) is rarely measured when evaluating women at high risk for breast cancer, but may offer insight into characterizing cancer risk. Patients enrolled in the University of Michigan Cancer Genetics registry for breast cancer evaluation were analyzed for personal and family history of cancer and features of PHTS. This group of women was compared to all women who had undergone PTEN testing and whether or not they met clinical criteria for PHTS. Among the 164 women referred for breast cancer risk evaluation, a statistically significant difference in mean HC was found between women who did (57.3 cm) and did not (55.4 cm) meet clinical criteria for PHTS with both values below the established threshold for macrocephaly (58 cm). The sensitivity and specificity of macrocephaly for the presence of a PTEN mutation were 100 and 53%, respectively, among the 28 women tested. The positive predictive value was 14%. PTEN mutation positive and PTEN mutation negative women were not well differentiated by PHTS clinical criteria (P = 0.2348). The high sensitivity of HC suggests that this simple measure can improve the detection of unrecognized patients with PHTS. Measuring HC is a useful clinical feature, but is insufficient as a singular screening tool for PHTS. Even in a high risk population, the PPV of this test is low. Diagnosis of this important genetic syndrome still relies heavily on detailed history and full physical exam.