What is Multiple Endocrine Neoplasia Syndrome 2 (MEN2) and how is it inherited?

MEN2 syndrome is inherited in an autosomal dominant pattern, and is caused by activating mutations in the RET proto-oncogene leading to the development of multiple endocrine tumours.

How does MEN2 syndrome present and what percentage develops malignancy?

The syndrome is divided into MEN2A, where patients develop:

• Medullary thyroid cancer in 95-100% of cases
• primary hyperparathyroidism, due to hyperplasia of multiple parathyroid glands (20%) and
• pheochromocytoma, in a percentage ranging from 60-100%

and in MEN2B characterized by growth of:

• aggressive medullary thyroid cancer, in almost all patients
• pheochromocytoma in half of the patients
• mucosal neuromas and intestinal ganglioneuromas
• skeletal deformities and
• characteristic facial features

How common is MEN2 syndrome and at what age does pheochromocytoma develop?

The incidence of the disease is 1 in 30,000 people. Depending on the mutation, pheochromocytoma can occur from the age of 8 with an average age, the age of 30. The majority of patients will develop pheochromocytoma in the other adrenal gland within a decade.

What should carriers do?

As medullary thyroid cancer can develop very early and is potentially life-threatening, prophylactic total thyroidectomy is recommended in the first months of life in new-borns with a confirmed mutation for MEN2B and in the first 5 years of life for MEN2A. In addition, as in other genetic syndromes, regular monitoring is mandatory.