Isolated multinodular goiter and follicular adenoma associated with a novel germline DICER1 variant: A benign...

DICER1 syndrome is a tumor-predisposition disorder caused by a germline pathogenic variant in DICER1. Pathogenic variants of DICER1 are the monogenic cause of various tumors including pleuropulmonary blastoma (PPB), ovarian sex cord-stromal tumors, and multinodular goiters. We present a family with a novel DICER1 pathogenic variant c.5528-2del who presents with development of isolated thyroid goiters/follicular adenoma. A 44 year old female presents with a past medical history of total thyroidectomy along with her 14-year-old son with a past history of multinodular thyroid goiter confirmed as multifocal follicular adenoma with papillary architecture and her 12-year-old daughter with a past history of multinodular thyroid goiter confirmed as diffuse nodular thyroid hyperplasia. No additional DICER1 syndrome presentations were observed. A genetics panel revealed that the mother, the 14-year-old son, and the 12-year-old daughter share a heterozygous DICER1 c.5528-2del variant, which has not been previously reported. In addition to our direct clinical observations from this family, genetic analysis via in silico prediction models, segregation analysis, and ACMG classification support this variant to be pathogenic. Given the absence of other DICER1 syndrome manifestations through human genetics evidence, this variant may be specifically associated with isolated multinodular goiters/follicular adenoma. Our findings contribute to the expanding genotype-phenotype correlation in DICER1 syndrome, providing new insights into its variable clinical presentation. Since not all variants are identical, reporting of these observations will advance precision medicine and benefit future patients through more accurate diagnosis, prognosis and personalized management strategies.