Pathogenic variants (disease-causing) in the RET gene cause multiple endocrine neoplasia type 2 (MEN2), a hereditary cancer syndrome characterized by a high risk for medullary thyroid carcinoma, pheochromocytoma (benign tumors of the adrenal gland that can become cancerous), and, in some individuals, hyperparathyroidism (overactive parathyroid glands). Other health conditions may occur in MEN2. Specific RET pathogenic variants correlate with the severity and age of onset, and some pathogenic variants warrant prophylactic thyroidectomy (removal of the thyroid) in childhood to prevent medullary thyroid cancer. Management focuses on lifelong, variant-specific surveillance that may include blood work, neck ultrasound, blood pressure and biochemical screening for pheochromocytoma, and targeted endocrine evaluations. RET pathogenic variants are not known to be more common in the Ashkenazi Jewish population.
MEN2 exhibits autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
Another name for this condition is Sipple syndrome.
Resources:
Association for Multiple Endocrine Neoplasia Disorders
Written December 2025
