Table 1.
Genetic syndromes associated with thyroid neoplasia
| Genetic syndrome | Genetic defect/inheritance | Clinical manifestations | Associated thyroid neoplasia |
|---|---|---|---|
| APC-associated polyposis (familial adenomatous polyposis, FAP, attenuated FAP, Gardner syndrome, Turcot Syndrome | Mutations of APC (5q21-q22) [particularly germline exon 15 mutations for thyroid cancer]/AD | Gastrointestinal polyposis (colon, duodenum, stomach), osteomas, nasopharyngeal angiofibroma, odontomas, congenital hypertrophy of retinal epithelium, epidermal cysts, fibromas, medulloblastoma, hepatoblastoma | PTC (cribriform-morular variant in 70–90% of patients with APC gene mutation)* |
| Carney complex, LAMB (lentigines, atrial myxoma mucocutaneous myxoma, blue nevi), NAME (nevi, atrial myxoma, myxoid neurofibroma, ephelide) |
Mutations of PRKAR1A [CNC1] (17q22-24) CNC2 (2p16)/AD |
Primary pigmented nodular adrenocortical disease), cardiac myxoma, skin myxoma, lentiginosis, blue nevi, breast ductal adenoma, Large-Cell calcifying Sertoli cell tumor, melanotic schwannoma, osteochondromyxoma |
Benign, non-toxic adenomas Multinodular goiter PTC (multiple, aggressive) FTC |
| DICER1 | Pathogenic germline variants of DICER1 (14q32.13, c.5441C > T) Rnase III endonuclease/AD | Pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig cell tumor of ovary, cervix embryonal rhabdomyosarcoma, Wilms tumor, ciliary body medulloepithelioma, nasal chondromesenchymal hamartoma |
Multinodular goiter (frequent) FTC (macrofollicular variant) Papillary adenoma Malignant teratomas Poorly differentiated carcinoma PTC, Carcinosarcoma |
| PTEN hamartoma tumor syndrome (Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, adult Lhermitte-Duclos, autism spectrum with macrocephaly) | Heterozygous germline pathogenic variants of 10q23.31 (phosphatase and tensin homolog)/AD | Macrocephaly, gastrointestinal hamartomas, macular pigmentation of the glans penis, multiple trichilemmomas, mucocutaneous neuromas, endometrial cancer, acral keratoses |
Multinodular goiter Adenomas Papillary thyroid carcinoma (follicular variant), 60% Follicular carcinoma (oncocytic [Hurthle cell]) 25–40% |
| Werner syndrome | Mutations in WRN [RECQL DNA helicase] (8p11.1–21.1)/AR | Premature aging syndrome, progeria-like, short stature, meningiomas, osteosarcomas |
PTC, FTC Anaplastic carcinoma (18% of Japanese patients develop thyroid cancer) |
| Multiple endocrine neoplasia (MEN) | MEN1 [Wermer] (11q13, menin)/AD | Hyperparathyroidism, pancreatic islet tumors, anterior pituitary tumors | Multinodular goiter, adenomas, carcinoma |
| MEN2A [Sipple] (RET codon 634)/AD | Pheochromocytoma, hyperparathyroidism, variants with cutaneous lichen amyloidosis or Hirschsprung disease, familial MTC | Medullary thyroid carcinoma | |
| MEN2B(3) [multiple mucosal neuroma syndrome] (RET codon 918)/AD | Multiple ganglioneuromas, marfanoid habitus, mucosal neuroma, pheochromocytoma | Medullary thyroid carcinoma | |
| MEN4 (CDNK1B) (very rare)/AD | Parathyroid and anterior pituitary, adrenal, gonadal tumors |