There are some genes that protect the human genome. Tumor suppressor genes act as guardians of the genome, preventing the development of neoplasia. The inactivation of these genes is a fundamental event in the pathogenesis of human cancer.1 In this sense, the armadillo repeat containing 5 (ARMC5) gene acts as a tumor suppressor gene.2, 3, 4 In vitro studies have shown that ARMC5 induces cellular apoptosis, whereas inactivation of ARMC5 abolishes this effect.5 Therefore, inactivation of ARMC5 could lead to resistance to apoptosis.

It has also been shown that germline mutations in the ARMC5 gene determine adrenal hyperplasia of adrenocortical cells with the development of nodules with hyperproduction of cortisol, which is a common cause of bilateral macronodular adrenal hyperplasia (BMAH). Theoretically, these mutations in the ARMC5 gene could also increase susceptibility to the development of other neoplastic processes, and the co-existence of other tumors in patients with BMAH has been described.6

The aim of the study is to present a family with 11 carriers of a novel mutation in the ARMC5 gene. Several carriers presented with BMAH: 2 with clinical Cushing's syndrome (CS), 2 presented with mild autonomous cortisol secretion (MACS) and 1 with autonomous cortisol secretion (ACS). Four carriers presented with malignant neoplasms: one prostate cancer and three obligate carriers (not tested) due to having offspring carrying the mutation who died of malignant neoplasms - carcinoma of the larynx, carcinoma of the stomach and carcinoma of the lung.