Gynecologic and reproductive health in patients with pathogenic germline variants in DICER1

Gynecol Oncol. 2020 Mar;156(3):647-653. doi: 10.1016/j.ygyno.2019.12.037. Epub 2020 Jan 15.


Objective: Germline pathogenic variation in DICER1 underlies a tumor-predisposition disorder with increased risk for cervical embryonal rhabdomyosarcoma and ovarian sex-cord stromal tumors, particularly Sertoli-Leydig cell tumors. The gynecologic and reproductive health of these females has not yet been described.

Methods: All female subjects recruited from November 2011 to July 2018 participating in an epidemiologic study of families with pathogenic DICER1 germline variation were included in this cross-sectional analysis. Participant evaluation included obstetric-gynecologic history, physical examination, hormone testing, pelvic ultrasound and record review.

Results: Of 64 females aged 2-72 years, fifteen underwent treatment for pleuropulmonary blastoma as children and three were treated for cervical embryonal rhabdomyosarcoma. Of nine patients reporting a history of ovarian tumors, all presented with virilization or amenorrhea; eight occurred in adolescence. Post-pubertal females with no history of ovarian tumors experienced normal pubertal development, reported regular menstrual cycles, were fertile and underwent natural menopause at median age of 52 years. Thirty-two of 33 women who tried to conceive successfully delivered liveborn children. Of these 32, 10 experienced pregnancy-related thyroid enlargement resulting in thyroidectomy within one year of pregnancy; nine others had undergone pre-pregnancy thyroidectomy.

Conclusion: In these DICER1-carrier females, DICER1-related gynecological tumors occurred during childhood or adolescence in some after which women generally experienced healthy reproductive lives. Individual education and screening for these tumors is warranted. The high rate of DICER1-related multinodular goiter resulting in pre- and post-pregnancy thyroidectomy underscores the importance of thyroid monitoring during pregnancy to ensure maternal and fetal wellbeing.

Keywords: Cervical embryonal rhabdomyosarcoma; DICER1-related multinodular goiter; Ovarian sex-cord stromal tumors; Pleuropulmonary blastoma; Sertoli-Leydig cell tumors of the ovary.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amenorrhea / genetics
  • Child
  • DEAD-box RNA Helicases / genetics*
  • Female
  • Genital Diseases, Female / genetics*
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • Ovarian Neoplasms / genetics
  • Pregnancy
  • Pulmonary Blastoma / genetics
  • Reproductive Health
  • Rhabdomyosarcoma, Embryonal / genetics
  • Ribonuclease III / genetics*
  • Uterine Cervical Neoplasms / genetics
  • Young Adult


  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

Supplementary concepts

  • Pleuropulmonary blastoma