FaCD Online Syndrome Fact Sheet

Last updated: 22 Feb 2011

Name: Familial Multinodular Goiter

Synonym: Adolescent Multinodular Goiter, incl. Multinodular Euthyroid Goiter & Non-Medullary Thyroid Cancer

Mode of Inheritance: AD / XL

Genes

DICER1, mapped to 14q31
MNG1, mapped to 14q
MNG2, mapped to Xp22
MNG3, mapped to 3q26.1-q26.3

Tumor features

thyroid adenoma
thyroid cancer, follicular
thyroid cancer, papillary
thyroid hyperplasia / goitre

Tumor features (possible)

rhabdomyosarcoma

Comment

Multinodular nontoxic goiter with areas of calcification and onset in adolescence or adulthood is the key feature of this disorder. Papillary thyroid cancer has been reported as a complication[1,2]. This is a genetically heterogenous disorder[3]. Clinically, there is overlap with familial non-medullary thyroid cancer. DICER1 germline mutations have been identified in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors, see DICER1 syndrome. Familial risks for hospitalized Graves' disease and goiter patients were studied in the Swedish population by Hemminki et al[5]. Calculated familial risk (SIR) for offspring of affected parents was 3.15 for nontoxic goiter. Familial risks were higher for affected siblings: 5.40 for nontoxic goiter.

Druker et al.[4] reported on a family with multinodular goiter (5 cases), follicular thyroid cancer (2 cases), Graves disease (1 case) and a paravertebral alveolar rhabdomyosarcoma in one of the goiter patients (aged 20 years).

References

[1] Bakhsh A, Kirov G, Gregory JW, Williams ED, Ludgate M. A new form of familial multi-nodular goitre with progression to differentiated thyroid cancer. Endocrine-related cancer 2006; 13(2):475-83.
[2] Tsilchorozidou T, Vafiadou E, Yovos JG, Romeo G, McKay J, Lesueur F, Bonora E. A Greek family with a follicular variant of familial papillary thyroid carcinoma: TCO, MNG1, fPTC/PRN, and NMTC1 excluded as susceptibility loci. Thyroid 2005; 15(12):1349-54.
[3] Bayer Y, Neumann S, Meyer B, Rüschendorf F, Reske A, Brix T, Hegedüs L, Langer P, Nürnberg P, Paschke R. Genome-wide linkage analysis reveals evidence for four new susceptibility loci for familial euthyroid goiter. The Journal of clinical endocrinology and metabolism 2004; 89(8):4044-52.
[4] Druker HA, Kasprzak L, Begin LR, Jothy S, Narod SA, Foulkes WD. Family with Graves disease, multinodular goiter, nonmedullary thyroid carcinoma, and alveolar rhabdomyosarcoma. Am J Med Genet 72[1], 30-33. 1997.
[5] Hemminki K, Shu X, Li X, Ji J, Sundquist K, Sundquist J. Familial risks for hospitalized Graves' disease and goiter. Eur J Endocrinol. 2009 Oct;161(4):623-9.