Multiple Endocrine Neoplasia Type 1

Background: Parathyroid disorders are very common in the general population and include disorders of parathyroid excess, deficiency, or defects in parathyroid hormone (PTH) signaling. PTH, the main secretory product of parathyroid glands is responsible for regulation of calcium-phosphate homeostasis. Objective: i) To investigate the cause of parathyroid disorders ii) To describe evolution, natural history, and longitudinal trends of parathyroid and related disorders seen in syndromic presentations like multiple endocrine neoplasia, hyperparathyroidism-jaw tumor syndrome Eligibility: People ages 6 months older who have, are at risk of having, or are related to a person with a parathyroid or related disorder. Design: Participants will be screened with a review of their medical records. Participants will be seen, tested, and treated by doctors based on their condition. Their visits may be in person or via telehealth. Participants will complete questionnaires. They will answer questions about their physical, mental, and social health. Participants may give samples such as saliva, blood, urine, or stool. Participants may give cheek cell samples. They will do this using a cheek swab or by spitting into a cup. Adult participants may give a skin biopsy. For this, a small bit of skin is removed with a punch tool. Participants may have medical photos taken. If participants have surgery during the course of their regular care either at the NIH or at a different hospital or doctor s office, researchers will ask for some of the leftover tissue. Participants will be in the study as long as they are being seen by their doctor.

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown in the Eligibility Section, you may enroll regardless of the results of your clinical genetic testing. While it is well recognized that hereditary factors contribute to the development of a subset of human cancers, the cause for many cancers remains unknown. The application of next generation sequencing (NGS) technologies has expanded knowledge in the field of hereditary cancer predisposition. Currently, more than 100 cancer predisposing genes have been identified, and it is now estimated that approximately 10% of all cancer patients have an underlying genetic predisposition. The purpose of this protocol is to identify novel cancer predisposing genes and/or genetic variants. For this study, the investigators will establish a Data Registry linked to a Repository of biological samples. Health information, blood samples and occasionally leftover tumor samples will be collected from individuals with familial cancer. The investigators will use NGS approaches to find changes in genes that may be important in the development of familial cancer. The information gained from this study may provide new and better ways to diagnose and care for people with hereditary cancer. PRIMARY OBJECTIVE: * Establish a registry of families with clustering of cancer in which clinical data are linked to a repository of cryopreserved blood cells, germline DNA, and tumor tissues from the proband and other family members. SECONDARY OBJECTIVE: * Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.

The goal of this observational study is to create, manage and analyze a retro-prospective multicenter national database of patients diagnosed with multiple endocrine neoplasia type 1 (MEN1) syndrome (including genetic, clinical and/or familiar diagnosis), aimed at collecting and studying anamnestic, diagnostic, genetic, clinical, and therapeutic data in a relatively high number of patients with this rare inherited endocrine tumor syndrome in Italy. The study will include 33 specialist clinical centers of endocrinology, pediatric endocrinology, pediatrics, and endocrine surgery, located throughout the Italian territory, and to which patients refer from all the 20 regions of Italy. Data will be collected over time, both in retrospective and prospective manners, during the 10-year average duration of the study, starting from the recruiting visit (basal visit) and then during each follow-up visits patients will undergo for the control of disease at the recruiting clinical centers, allowing for an epidemiological evaluation of prevalence and incidence of MEN1 in Italy, collecting detailed clinical history of the disease in enrolled patients, and refining and deepening medical knowledge in the field of this rare inherited endocrine tumor syndrome, and, thus, to be able to define optimal tailored diagnostic, clinical, and therapeutic management of patients, improving their quality of life. Collected data will include both the most classic traits of the pathology and the less common ones. The main aspects this observational study aims to assess and clarify are: 1. Evaluation of prevalence and incidence of MEN1 in Italy. 2. Clinical characterization of MEN1 phenotypes, through both cross-sectional and longitudinal analyses of collected data, and also based on MEN1 mutation types and location. 3. Evaluation of the over time prevalence of bone mass loss, osteopenia, osteoporosis and fragility fractures in patients with MEN1, with and without primary hyperparathyroidism, globally and also based on gender and age. 4. Over time evaluation of responses to surgical and pharmacological therapies in in patients MEN1. 5. Evaluation of dietary habits in MEN1 patients, by filling out a specific questionnaire at the time of the study recruitment. 6. Evaluation of quality of life and accessibility to specialist medical centers and to surgical and pharmacological therapies on the Italian territory by patients affected by MEN1 syndrome, globally and according to the region of residence, by filling out a specific self-evaluation questionnaire at the time of the study recruitment. The study will include a single cohort of female and male patients of any age, diagnosed with MEN1 syndrome (including either genetic, clinical and/or familiar diagnosis). The study does not include either any control group/comparison group or healthy volunteers. The study itself does not involve any medical intervention or drug administration. Surgical and pharmacological treatments for which data on response to therapy will be collected in the database, are those commonly employed for the control/treatment of MEN1 tumors and related symptoms, regardless of patients' inclusion in this observational study.

Patients with the Multiple Endocrine Neoplasia type 1 (MEN1) syndrome are genetically predisposed for developping multiple pancreatic neuro-endocrine tumours (pNET). The management of small (pNET) in both MEN1 and sporadic cases, pose a major clinical challenge. At present, pancreatic surgery is the only curative treatment but it is associated with high morbidity. To reduce the morbidity ascosiated with surgery and thereby potentially improve quality of life for MEN1 patients introduction of less invasive techniques for treatment of pNET is important. High-dose-high precision MR-guided radiotherapy (MRgRT) holds promise as a new less invasive treatment option for pNET. The aim of this study is to assess efficiacy and safety of MRgRT for treatment of pNET in MEN1 patients.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of lesions derived from cells with the ability to produce hormones that may arise from multiple different organs. Their clinical behavior is quite variable, encompassing both benign lesions and aggressive tumors that invade surrounding and/or distant structures. NENs may also cause serious morbidity due to hormone oversecretion. NENs are among the most frequently inherited human tumors, presenting either isolated or as part of syndromes in which a single patient or family develops multiple tumors. There are also non-inherited changes in the genetic information of the tumor cells that are potential targets for treatment. Both inherited and non-inherited DNA defects can be identified using modern routine genetic tests which, unfortunately, are not widely available in Mexico. This project seeks to uncover the genetic defects causing NENs in a large cohort of Mexican patients, using three different methods for genetic testing. Adult individuals with various types of NENs from two reference hospitals in Mexico City will be invited to participate. After completing informed consent, blood and, if possible, tissue samples will be obtained from all participants. Clinical details, laboratory results, imaging studies, and histopathological data at disease presentation will be retrieved. An initial screening will be performed by analyzing changes in the sequence of multiple genes that have been associated with the occurrence of NENs. In cases with negative screening, a specific method to assess changes in the number of copies of the same genes will also be employed. Finally, sequences of all DNA regions encoding information required to make proteins will be obtained in selected cases. Analyses will be carried out in blood and, if available, also in tumor tissue samples from study participants. Screening of additional family members will be offered. This project will accurately describe the repertoire of specific defects causing NENs in the study population, and will likely uncover and characterize novel genetic associations. The results will contribute for a better understanding of the alterations within and outside known driver genes that shape syndromic presentations, tumor behaviors, and inheritance patterns in individuals with NENs. These data will contribute to improve the information on the molecular bases of NENs, including alterations that can be used as therapeutic targets.