Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation.
Keywords: cascade genetic screening; hyperparathyroidism; multiple endocrine neoplasia type 1; pancreatic neuroendocrine tumor; pituitary tumor.