Genetics and Epigenetics of Recurrent Hydatidiform Moles: Basic Science and Genetic Counselling

Curr Obstet Gynecol Rep. 2014 Jan 21;3(1):55-64. doi: 10.1007/s13669-013-0076-1. eCollection 2014.


Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal hyperproliferation of trophoblastic cells, which derive from the trophectoderm, the outer layer of the blastocyst that would normally develop into the placenta during pregnancy. GTDs encompass hydatidiform mole (HM) (complete and partial), invasive mole, gestational choriocarcinoma, placental-site trophoblastic tumor, and epithelioid trophoblastic tumor. Of these, the most common is HM, and it is the only one that has been reported to recur in the same patients from independent pregnancies, which indicates the patients' genetic predisposition. In addition, HM is the only GTD that segregates in families according to Mendel's laws of heredity, which made it possible to use rare familial cases of recurrent HMs (RHMs) to identify two maternal-effect genes, NLRP7 and KHDC3L, responsible for this condition. Here, we recapitulate current knowledge about RHMs and conclude with the role and benefits of testing patients for mutations in the known genes.

Keywords: DNA methylation; Epigenetics; GTD; Genetics; Gestational choriocarcinoma; Gestational trophoblastic disease; KHDC3L; Live birth; Management of gestational trophoblastic diseases; NLRP7; Recurrent HMs (RHMs); Recurrent hydatidiform moles.

Publication types

  • Review