Mutations in the DICER1 gene may lead to DICER1-related disorder, a rare familial tumor susceptibility syndrome that confers increased risk most commonly for:
- pleuropulmonary blastoma (PPB)
- ovarian sex cord-stromal tumors (Sertoli-Leydig cell tumor [SLCT], juvenile granulosa cell tumor [JGCT], and gynandroblastoma);
- cystic nephroma (CN)
- thyroid gland neoplasia (multinodular goiter [MNG], adenomas, or differentiated thyroid cancer).
Even more rarely observed tumors are ciliary body medulloepithelioma (CBME); botryoid-type embryonal rhabdomyosarcoma (ERMS) of the cervix or other sites; nasal chondromesenchymal hamartoma (NCMH); renal sarcoma; pituitary blastoma; and pineoblastoma. Novel phenotypes continue to be discovered. The majority of tumors in families with a DICER1 germline pathogenic variant occur in individuals younger than age 40 years. PPB, a neoplasm that arises during lung development or shortly after birth, typically presents in infants and children younger than age six years. Age of onset of ovarian sex cord-stromal tumors is not well defined. CN presents in children younger than age four years.Gene Reviews
DICER1-related disorders are inherited in an autosomal dominant manner, and more than 180 mutations are known. The ClinGen Actionability Working Group has a summary of recommended actions here.