Table 5.

Genetic syndromes associated with thyroid neoplasia

Inherited tumor syndrome	Germline pathogenic variant and mode of inheritance	Type of thyroid neoplasia	Syndromic features noted on clinical examination (listed in approximate order of appearance; some features only appear in adulthood)	Additional clinical features
Familial adenomatous polyposis (FAP) (includes Gardner syndrome and Turcot syndrome)	APC Autosomal dominant 20% cases arise de novo	Cribriform–morular cancer	Congenital hypertrophy of the retinal pigment epithelium (CHRPE), congenital absence of teeth, delayed eruption of teeth, dentigerous cysts, supernumerary teeth, odontomas, epidermoid cysts, fibrous dysplasia of the skull, mandibular osteomas, fibromas, desmoid tumors, and pilomatricomas.	Hepatoblastoma, medulloblastoma, multiple adenomatous polyps throughout the gastrointestinal tract, principally affecting the colon with high likelihood of malignant transformation, as well as upper GI tract adenomas and adrenal adenomas.
Carney complex	PRKAR1A Autosomal dominant 30% cases arise de novo	Papillary thyroid cancer, follicular adenoma, and follicular thyroid cancer	Pale brown to black lentigines of skin, lips, and oral mucosa, soft tissue myxomas, Schwannomas, and epithelioid-type blue nevi.	Benign adrenal tumors (primary pigmented nodular adrenocortical disease), pituitary tumors (often somatotropinomas), large cell calcifying Sertoli cell tumors, breast ductal adenoma, osteochondromyxoma, and psammomatous melanotic Schwannoma of the nerve sheath.
DICER1 syndrome	DICER1 Autosomal dominant	Multinodular goiter, papillary thyroid cancer, and poorly differentiated carcinoma	Macrocephaly (OFC > 97th centile).	Pleuropulmonary blastoma, ovarian Sertoli–Leydig cell tumors, cystic nephroma, ciliary body medulloepithelioma, botryoid-type embryonal rhabdomyosarcoma, nasal chondromesenchymal hamartoma, pituitary blastoma, pineoblastoma, Wilms tumor, and juvenile intestinal hamartomas.
PTEN Hamartoma tumor syndrome (PHTS) (includes Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, and PTEN-related Proteus syndrome)	PTEN Autosomal dominant Over 10% of cases arise de novo	Multinodular goiter, follicular adenoma, papillary thyroid cancer (classical and follicular variant) Follicular thyroid cancer (FTC cases are more common than PTC)	Macrocephaly (OFC > 97th centile) and dolichocephaly, learning difficulties, autism and developmental delay, lipomas, vascular features including hemangiomas and arteriovenous malformations, gingival hypertrophy, oral papillomas, facial papules, acral keratoses, palmoplantar keratosis, trichilemmomas, pigmented macules of the glans penis, and overgrowth of tissues.	Benign and malignant tumors of the breast, colon, endometrium, and kidney, adult Lhermitte–Duclos disease due to cerebellar dysplastic gangliocytoma.
Werner syndrome	WRN Autosomal recessive	Papillary thyroid cancer, follicular thyroid cancer, and anaplastic thyroid cancer	Short stature (lack of pubertal growth spurt), cataracts, premature aging, tight atrophic skin, ulceration, hyperkeratosis, pigmentary alterations, regional subcutaneous atrophy, and characteristic ‘bird-like facies’, hypogonadism, secondary sexual underdevelopment, premature greying and thinning of scalp hair, pes planus, and abnormal voice.	Malignant melanoma, meningioma, soft tissue sarcomas, leukemia and pre-leukemic conditions of the bone marrow, primary bone neoplasms, osteoporosis, soft tissue calcification, evidence of premature atherosclerosis, and diabetes mellitus.

Table 4 in the 2015 ATA Pediatric Guidelines (8) formed the basis for this table.