FaCD Online Syndrome Fact Sheet

Last updated: 19 Mar 2008

Name: Familial Non-Medullary Thyroid Cancer

Synonym: FNMTC, incl.: Familial Thyroid Tumors with Cell Oxyphilia, Familial Papillary Thyroid Microcarcinoma, Familial Papillary Thyroid and Renal Carcinoma

Mode of Inheritance: multifact?/ AD?

OMIM number: 188550 603744 603386

Genes

NMTC1, mapped to 2q21
PTCPRN/PRN1#, mapped to 1q21
TCO#, mapped to 19p13.2

Tumor features

papillary thyroid microcarcinoma
renal cell cancer, papillary
thyroid cancer, anaplastic
thyroid cancer, follicular
thyroid cancer, papillary
thyroid hyperplasia / goitre
thyroid tumor with cell oxyphilia (benign and malignant)

Tumor features (possible)

colorectal cancer
endometrial cancer
gastric cancer
parathyroid adenoma
renal oncocytoma
Wilms' tumor (nephroblastoma)

Non-tumor features (possible)

hyperparathyroidism

Comment

FNMTC occurs in approximately 4 % of patients with differentiated thyroid cancer[1] and in 6% of patients with papillary thyroid microcarcinoma[2]. Charkes[3] calculated that approximately 45% of all paired familial cases are due to chance, the remainder being probably genetic. Clustering of 3 or more cases can be explained by chance in less than 0.1% of cases. Of FNMTC cases, the papillary, follicular and anaplastic varieties account for approximately 91%, 6% and 2 % respectively. These cases manifest approximately 10 years earlier than their sporadic counterparts. An increased occurrence of other tumors have been reported in these families: mainly gastric cancer, colorectal cancer, uterine and renal cell cancer[1;4;18,19,21]. A study in the Swedish family cancer database demonstrated a familial relative risk for papillary thyroid cancer carcinoma of approximately 3 in case of a parent with NMTC and of 6 in case of an affected sibling. Among sisters risk was 11. In general, risks were highest for early onset cancers.[20]

As a group, FNMTC is genetically heterogenous. Of all FNMTC cases, familial papillary thyroid cancer may be a true genetic entity[5-7]. FNMT-micro-adenocarcinomas may be more common than previously suspected[8] and Lupoli et al.[2] have suggested that familial papillary thyroid microcarcinoma is a distinct clinical entity with a worse prognosis than that of sporadic papillary thyroid cancer.
Oxyphilic tumors of the thyroid have been reported to occur occasionally in familial clusters[9]. Canzian et al.[10] recently mapped the gene for familial thyroid tumors with cell oxyphilia to 19p13.2 (TCO locus). Thyroid histology in a TCO-linked family has been reported by Harach et al.[11].
No germline mutations in RET, TP53[12] or linkage to the familial nontoxic multinodular goiter (MNG1) locus[13;14] or TCO locus[14] have been found in groups of FNMTC families. The TCO and MNG1 locus were excluded in a large family with familial papillary thyroid carcinoma[15]. There is clinical overlap with familial multinodular goiter, which may be associated with NMTC.

A large 3-generation family presenting with papillary carcinoma of the thyroid as well as the kidney (including a multifocal case) was reported by Malchoff et al.[16]. One of the family members was diagnosed with a renal oncocytoma. The authors mapped the disorder in this family to 1q21.

Rone et al.[17] stressed that the combination of hyperparathyroidism/parathyroid adenoma and thyroid tumors does not suggest MEN2A (which only in rare cases has been associated with NMTC): the association of NMTC and parathyroid adenomas has been repeatedly reported in sporadic cases (4-7 % of patients undergoing parathyroidectomy apparently have NMTC.

Some studies have suggested a worse prognosis for familial NMTC compared to sporadic cases[22,23], however, other studeis show no difference[24].

References