Multiple endocrine neoplasia type 1 (MEN1) is characterized by endocrine tumors, particularly in the parathyroid glands, anterior pituitary, and pancreatic islet cells. Primary tumors may be found in more than one endocrine organ and/or multiple tumors may be found in the same organ. The presence of MEN1-associated endocrine tumors causes an array of clinical and biochemical manifestations secondary to hormone hypersecretion: hyperparathyroidism [the most frequent MEN1-symptom with potential central nervous (CNS), hypercalcemia, gastrointestinal, renal cardiovascular, and skeletal involvement), hypercortisolism, gigantism and acromegaly, prolactinoma (with associated oligomenorrhea, amenorrhea, and galactorrhea in females and sexual dysfunction in males), gastrinoma, and insulinoma. Non-endocrine tumors also are common and can include facial angiofibromas and collagenomas of the skin, lipomas, meningioma and ependymoma of the CNS, and skin collagenomas, and leiomyomas. Mutations in the MEN1 gene are highly penetrant; approximately 50% of MEN1 mutation carriers are symptomatic by age 20 and 95% are symptomatic by age 40.
Familial Isolated Hyperparathyroidism (FIHP) is characterized by parathyroid adenoma/hyperplasia (and possibly carcinoma) in the absence of other associated endocrinopathies, is also associated with mutations in the MEN1 gene. However, FIHP is genetically heterozygous and can be cause by mutations in other genes, such as CASR and HRPT2.
Carrier testing reasons for referral:
1. Testing parents of a child with a specific dominant mutation, in order to determine if the mutation in the child is new or inherited.
2. Carrier testing in parents of a child with apparently homozygous recessive mutations, to rule out the possibility that the child has one mutated allele and one allele that is deleted or refractory to amplification.
3. Carrier testing in the parents of a child with recessive mutations, to confirm that all four parental alleles can be detected prior to prenatal diagnosis.
4. Pre-symptomatic testing in siblings of the index case.
5. Carrier testing in the extended family.
Lab Staff: Send whole blood in original collection container labeled with patient name, date of birth and medical record number, including signed consent form and requisition, with a cool pack during warm temperatures, via overnight or second-day courier so that the sample will arrive at GeneDx, Inc. on a weekday (Monday through Friday). Samples drawn on Friday or Saturday should be held at refrigerated temperatures for shipment on Sunday. Do not freeze.
Note: Specimens may be stored at refrigerated temperatures for up to 7 days prior to shipping.