Syndrome

Mutated gene

Manifestations

MEN1

MEN1

Primary hyperparathyroidism (usually four-gland hyperplasia), anterior pituitary adenomas, tumors of endocrine pancreas and duodenum, foregut carcinoids

MEN subtype 2A

RET proto-oncogene

Medullary thyroid cancer, pheochromocytoma, primary hyperparathyroidism (usually single adenoma), cutaneous lichen amyloidosis, Hirschsprung disease

MEN subtype 2B

RET proto-oncogene

Medullary thyroid cancer, pheochromocytoma, marfanoid body habitus, facial features resulting from mucosal neuromas, ganglioneuromatosis of the gastrointestinal tract

Familial medullary thyroid cancer

RET proto-oncogene

Medullary thyroid cancer in at least four family members, with documented absence of other endocrinopathies

Hyperparathyroidism-jaw tumor syndrome

HRPT2

Primary hyperparathyroidism (usually single adenoma), ossifying fibromas of maxilla or mandible, renal cysts and hamartomas, 15% risk of parathyroid carcinoma

Familial isolated hyperparathyroidism

MEN1, HRPT2, CASR, other

Nonsyndromic primary hyperparathyroidism

Familial hypocalciuric hypercalcemia

CASR

Benign hypercalcemia; medical management only

von Hippel-Lindau syndrome (VHL)

VHL

Pheochromocytoma, retinal and central nervous system hemangioblastoma, renal cysts and clear cell carcinoma, pancreatic cysts and islet cell tumors, endolymphatic sac tumors, papillary cystadenomas of the epididymis and broad ligament

Familial pheochromocytoma/ paraganglioma syndrome

SDHB, SDHC, SDHD

Multiple paragangliomas and pheochromocytoma

Neurofibromatosis type I

NF1

Pheochromocytoma, characteristic physical features (eg, café-au-lait spots, neurofibromas, axillary and inguinal freckling)

Cowden syndrome

PTEN

Nonmedullary thyroid cancer (usually follicular rather than papillary); benign and malignant tumors of skin, oral mucosa, breast, and uterus

Familial adenomatous polyposis

APC

Hundreds of adenomatous colon polyps, colon cancer, cribriform morular variant of papillary thyroid cancer

Carney complex

PRKAR1A

Endocrine tumors (including thyroid, pituitary, primary pigmented nodular adrenocortical disease), characteristic skin pigmentation, myxomas, melanotic schwannomas

Familial nonmedullary thyroid cancer

Unknown

Nonsyndromic nonmedullary thyroid cancer