Endocrine Abstracts

Background: Pathogenic germline DICER1 variants cause an hereditary cancer predisposition syndrome with a variety of manifestations: in addition to first described pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumours, individuals may also develop benign (multinodular goiter MNG, cystic nephroma.) or malignant tumours as differentiated thyroid carcinoma from infancy to adolescence and early adult.

Objective: To investigate the specificity of DICER1-families exhibiting only thyroid manifestation across generations.

Methods: We report a series of 6 families whose diagnosis for Dicer1 syndrome was done on childhood MNG or in index patient or in siblings presenting benign or malignant thyroid tumours only. We screened DNA and thyroid tissue samples from probands and families’ members for DICER1 variants or associated variants using Next Generation Sequencing tools for these families with thyroid specific manifestations of the syndrome. Patients’ and family history, clinical examination, thyroid ultrasonography, thyroid function were evaluated and related to histology and somatic variant analysis when available.

Results/Discussion: In all cases the DICER1 pathogenic variants associated to thyroid manifestation have been already described in the literature or located in the enzymatic site of the enzyme. Additional somatic variants were identified for half of the families. We discuss the management of these families in the context of international recommendations and genetic counselling.