Single center experience in genetic testing of suspected MEN1 and MEN2 syndromes

Abstract

Background/Objectives: Multiple endocrine neoplasia type 1 and 2 (MEN1 and MEN2) syndromes are genetic predisposition of various endocrine system tumours like thyroid cancer, pheochromocytoma, parathyroid tumours and others. Early detection of such syndromes allows better management as early screening and interventions are possible. Methods: We report the experience of Hospital of Lithuania Health Science University Kauno klinikos in genetic testing of suspected MEN1 and MEN2 cases in a time period between 2016 - 2021. Sanger sequencing of RET (NM_020975.4) or/and MEN1 (NM_130799.2) gene coding regions was performed. Results: 18 patients were referred to geneticist due to medullary thyroid cancer. The mean age at which they developed cancer was 48.8. In our study 3 cases had pathogenic variants in RET gene c.1833C>G; c.1900T>C, c.2753T>C and were diagnosed with first cancer at 31,37 and 16 years of age, respectively. 9 cases of pheochromocytoma, with mean age at diagnosis 42.3, had no pathogenic variants in RET gene. A case of hyperparathyroidism in 14 years old patient showed no pathogenic variants in RET and MEN1 genes. One female patient was referred to due to early prolactinoma at 30 years of age. Later on she was also diagnosed with insulinoma and hyperparathyroidism. She had a novel c.446-2A>T variant in MEN1 gene which on RNA Sanger sequencing showed exon skipping and was classified as pathogenic. Conclusion: In 5 years we have diagnosed 4 MEN syndrome cases what lead to better understanding of patient secondary tumour risk and the need of family screening.