Multinodular goiter (MNG) is a common disorder characterized by nodular enlargement of the thyroid gland. In MNG1, some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary (summary by Rio Frio et al., 2011).
... Multinodular goiter (MNG) is a common disorder characterized by nodular enlargement of the thyroid gland. In MNG1, some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary (summary by Rio Frio et al., 2011). - Genetic Heterogeneity of Multinodular Goiter Other MNG loci map to chromosome Xp22 (MNG2; 300273) and chromosome 3q26 (MNG3; 606082).
Murray et al. (1966) described a family in which members of 5 generations had nontoxic goiter appearing in the early teens. Calcification and firm, nodular consistency were unusual features. None of the known defects in thyroid hormonogenesis could ... Murray et al. (1966) described a family in which members of 5 generations had nontoxic goiter appearing in the early teens. Calcification and firm, nodular consistency were unusual features. None of the known defects in thyroid hormonogenesis could be demonstrated. Radioactive iodine studies showed increased thyroid avidity and rapid turnover. No certain male-to-male transmission was observed. Jensen et al. (1974) described ovarian tumors in a mother and 2 daughters. The tumor proved to be arrhenoblastoma, secreting androgens, in the 2 daughters. Thyroid adenomas occurred in several members of the family and were found to be associated frequently with ovarian arrhenoblastoma in young women surveyed separately. O'Brien and Wilansky (1981) described a family in which the 16-year-old proband had a nodular thyroid and a functioning ovarian arrhenoblastoma. Males and females to a total of 6 in 4 generations were known to have nodular thyroids. The disorder was apparently transmitted through an unaffected male. The authors raised the question of testicular tumors in males with the gene. Couch et al. (1986) observed a Canadian family in which 18 members had a form of euthyroid adolescent multinodular goiter. Histologic study showed multiple adenomata with areas of epithelial hyperplasia, hemorrhage, and calcification. In 2, there were focal areas of epithelial hyperplasia reminiscent of low-grade papillary carcinoma (see 188550). The family was later studied by Bignell et al. (1997) (see MAPPING). Druker et al. (1997) reported a family of Ashkenazi Jewish descent in which 7 individuals had benign and/or malignant thyroid tumors. The proband was diagnosed with nodular hyperplasia and superimposed well-differentiated localized follicular carcinoma of the thyroid at age 17. Her father also had multinodular goiter and was later diagnosed with well-differentiated follicular carcinoma. Three of the proband's sibs had thyroid conditions, including 2 with multinodular goiter and 1 with an enlarged thyroid; 1 of the sibs died of an alveolar rhabdomyosarcoma at age 20 years. Niedziela (2008) reported a 14-year-old girl with an ovarian Sertoli-Leydig cell tumor and high serum testosterone. She presented with intermittent abdominal pain, deepening of voice, and amenorrhea for 4 months. She had a personal and family history of multinodular goiter. After surgery and treatment of both, the patient remained disease-free for 6 years.
In affected members of 5 unrelated families with autosomal dominant multinodular goiter with or without Sertoli-Leydig cell tumors, Rio Frio et al. (2011) identified 5 different heterozygous mutations in the DICER1 gene (see, e.g., 606241.0007-606241.0010). Four of the ... In affected members of 5 unrelated families with autosomal dominant multinodular goiter with or without Sertoli-Leydig cell tumors, Rio Frio et al. (2011) identified 5 different heterozygous mutations in the DICER1 gene (see, e.g., 606241.0007-606241.0010). Four of the families had previously been reported by O'Brien and Wilansky (1981), Niedziela (2008), Bignell et al. (1997), and Druker et al. (1997). Studies of both types of tumors from several families showed no loss of heterozygosity at the DICER1 locus. Goiter tissue showed mixed immunostaining results, with some tissues showing no DICER1 protein staining and other tissues showing clear cytoplasmic staining. RNA studies from patient lymphoblasts showed perturbations of miRNA compared to controls, suggesting a dysregulation of gene expression patterns. In particular, LET7A (605386) and miR345 were both decreased in DICER1-related goiter tissue.