Multiple endocrine neoplasia 1 (MEN1) or Wermer’s Syndrome is an autosomal dominant disorder caused by germ line mutations in the
MEN1 gene located in the region 11q13.1 [
1].
MEN1 is a tumor suppressor gene that encodes for the protein, Menin. This 610 amino acid protein is localized within the nucleus, has two functional nuclear localization signals and represses JunD mediated transcription. It is expressed in a variety of tissues and is conserved across species from Drosophila to
Homo sapiens. Menin is proposed to act as a tumor suppressor, as
MEN1-associated tumors follow Knudson’s “two-hit hypothesis” [
2,
3]. MEN1 is characterized by the presence of a combination of tumors of the parathyroid glands, anterior pituitary, and Islet cells of the pancreas. In addition, tumors of the adrenal cortex, facial angiofibromas, carcinoid tumors, collagenous tumors, and lipomatous tumors have also been described. A clinical diagnosis of MEN1 is made in cases where there is occurrence of two or more primary MEN1 tumor types, or where there is one of the MEN1-associated tumors and a family member with a clinical diagnosis of MEN1. About 10–20% patients with familial MEN1 do not have a detectable pathogenic variant in the
MEN1 gene [
4]. The MEN1 phenotype is highly variable even within families and no genotype-phenotype correlations have been made to date [
5]. The clinical presentation and age of diagnosis vary by the type of tumor. Primary hyperparathyroidism is the most common first presentation in patients with MEN1, followed by Pancreatic Neuroendocrine Tumors (pNET) and Pituitary tumors (PIT) [
6]. In fact, primary hyperparathyroidism is diagnosed in a majority of patients before the diagnosis of MEN1. The age of diagnosis varies from the first to the fifth decade, median age being 37 years for patients with MEN1 pathogenic variants and 55 years for patients without MEN1 pathogenic variants [
6].
In this report we describe a case of MEN1 where diagnosis of hyperparathyroidism in family members prompted the 76 years old asymptomatic proband to seek a genetics referral. The report expands on the phenotype of this syndrome and also highlights the phenotypic variability associated with it.