Introduction: Multinodular goiter (MNG) is a common disorder of the thyroid gland, characterized by thyroid enlargement due to the development of multiple hyperplastic nodules. It is infrequent in children. Here, we present the case of two families with novel DICER1 mutations and familial history of nodules in adolescence.
Observations: A 10-year-old female presented a MNG. TSH, Free T3, Free T4 were in the normal range and thyroid autoantibodies were negative. Familial history included an MNG operated at the age of 15 in her brother and at the age of 19 in her father. Fine needle cytology of the thyroid was of undetermined significance. She underwent a thyroidectomy, and histology revealed a benign follicular adenoma. Based on familial history and young age, a hereditary predisposition syndrome was suspected and genetic testing of DICER1 was undertaken. An heterozygous germ-line DICER1 variant was identified in Exon 4 (c.322C>T, p.Gln108Stop). This variant was predicted to be deleterious with a premature stop codon and the loss of protein function. A 2-year-old girl presented a pleuropulmonary blastoma. Familial history showed that her mother had a left unilateral retinoblastoma at the age of three, and thyroid nodules leading to a thyroidectomy at the age of 15, and that her sister also had a thyroidectomy at the age of 7 for nodules. Genetic screening of DICER1 showed an heterozygous germ-line mutation in Exon 17 (c2692del, p.Glu898Lysfs*10) in the girl and her mother.
Discussion: Thyroid nodules and MNG are uncommon in pediatric population. Familial cases, or the association with familial tumors, should prompt the search for DICER 1 mutation. DICER1 syndrome is a pediatric cancer predisposition condition causing a variety of tumor types in children and young adults. Recent recommendations have been established for detecting pleuropulmonary blastoma, ovarian sex cord-stromal tumors and other DICER1-associated tumors.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology