Genetics of trophoblastic diseases

SOGC/GOC Clinical Guideline #408, January 2021

  • CHMs (diploids) are generally characterized by the absence of a haploid set of maternal chromosomes and the presence of 2 haploid sets of paternal chromosomes.
  • PHMs (triploids) result from a similar process, but contain 1 haploid set of maternal chromosomes, resulting in a triploid pregnancy (69XXX, 69XXY, or 69XYY).
  • A triploid (non-molar) pregnancy has 2 sets of maternal chromosomes and only 1 haploid set of paternal chromosomes.
  • Immunohistochemical staining for the p57 KIP2 CDKN1C gene can be used to differentiate CHMs from PHMs and dropsical abortions.
  • CDKN1C gene is a maternally expressed paternal imprint gene.
  • The p57 KIP2 is entirely absent from the MHC villous trophoblast due to its androgenetic origin.
  • The autosomal recessive hereditary disease affects the NLRP7 or KHDC3L genes (50-80% biparental diploid CHM).
  • Postpartum CC is usually composed of biparental chromosomes identical to those of the fetus, while CC after a full mole is androgenetic.
  • Non-gestational CCs are rare and can be distinguished by the absence of paternal DNA.

2021. Guideline No. 408: Management of Gestational Trophoblastic Diseases. Eiriksson L, Dean E, Sebastianelli A, Salvador S, Comeau R, Jang JH, Bouchard-Fortier G, Osborne R, Sauthier Ph. J Obstet Gynaecol Can;43(1):91-105.

Complete mole : paternal material only, p57 negative, diploid

Partial mole : paternal and maternal material, p57 positive, triploid

Roles of genes in recurrent moles

  • The NLRP7 gene, (19q13.4), CATERPILLER family (Tschopp, 2003) is involved in apoptosis and inflammation. there is also a causal role in MH and recurrent abortions (Murdoch, 2006).
  • Bi-allelic deleterious mutations have also been detected in the MEI1, TOP6BL/C11orf80 and REC114 genes (Slim, 2020).
  • An anomaly of the HFM1 gene also suggests a role in primary ovarian failure and in recurrent moles (Slim, 2023).
  • The risk of mole recurrence after a first recurrence is 1% and 16-28% after 2 recurrences.

Modified on 12/23/2023