Publication:

Recurrent hydatidiform mole: a case report highlighting NLRP7 gene mutations and genetic imprinting

Recurrent hydatidiform mole (RHM) is a rare form of gestational trophoblastic disease and is frequently associated with mutations in maternal-effect genes, particularly NLRP7, which play a critical role in early embryonic development and genomic imprinting. We report the case of a 26-year-old woman (G7P0) who presented at 9 weeks’ gestation with features suggestive of a complete molar pregnancy. Ultrasonography demonstrated a heteroechoic intrauterine mass, and serum β-human chorionic gonadotropin levels were markedly elevated at 272,600 IU/l. Her obstetric history was significant for 6 prior molar pregnancies, highlighting the recurrent nature of the condition; one of these pregnancies progressed to low-risk gestational trophoblastic neoplasia with pulmonary metastases, which was successfully managed with multiagent chemotherapy and close follow-up. In view of the recurrent disease, genetic evaluation was undertaken and revealed compound heterozygous pathogenic variants in the NLRP7 gene, including an exon 3 deletion and an exon 4 truncation. The patient received comprehensive counseling regarding the genetic etiology of her condition, its oncologic implications, and future reproductive options. Biallelic NLRP7 mutations result in abnormal oocyte development and impaired genomic imprinting, leading to recurrent molar gestations and a significantly reduced likelihood of achieving a viable pregnancy with autologous oocytes. Ovum donation remains the most viable reproductive option for affected women. This case underscores the importance of early genetic evaluation in women with recurrent molar pregnancies to guide individualized management, surveillance, and reproductive counseling.