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Multiple Endocrine Neoplasia type 1 (MEN1) is a rare hereditary cancer syndrome marked mainly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first-degree relative showing one of the characteristic endocrine tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, and collagenomas have been described. The syndrome is transmitted as an autosomal dominant trait. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. MEN1 maps to chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, which shows no sequence homology to other known human proteins. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair, and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving knowledge of the molecular genetics of the syndrome, has led to progress in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, for whom routine surveillance (regular biochemical and/or radiological screening to detect the development of MEN1-associated tumours and lesions) is recommended. |