Prenatal Diagnosis of Severe Factor VII Deficiency in the Setting of Maternal Breast Cancer

Congenital factor VII (FVII) deficiency is the most common rare bleeding disorder (RBD), presenting with various clinical manifestations. Given the heightened risk of life-threatening bleeding and fatal hemorrhagic complications, prompt detection of the disorder is critical, especially in cases with low FVII levels and a history of familial severe clinical presentations. In such cases, prenatal diagnosis (PND) emerges as a life-saving option. In this study, we reported two PNDs in a family with a positive family history of severe FVII deficiency (<1%) and a positive history of breast cancer in the mother at the time of the second PND. Sanger sequencing of the entire F7 gene was performed to detect the underlying gene variant in the affected girl and her parents. An FVII activity assay was performed to determine the plasma FVII levels in the girl and her parents. Chorionic villus sampling for fetal DNA acquisition was performed. DNA extraction and polymerase chain reaction (PCR)-sequencing of exon 1 of the F7 gene were performed on fetal DNA samples. An FVII activity assay was performed on the neonate to determine the severity of FVII deficiency. In the next two years, clinical presentations of the two children were collected. Molecular analysis revealed the c.1A>G (p.Met1Val) variant in exon 1 of the affected girl, who was homozygous for this variant in the F7 gene and had severe FVII deficiency (<1%). Both parents were heterozygous for this variant, with FVII levels of 33% and 50% in the mother and father, respectively. PND revealed that both fetuses were homozygous for the c.1A>G variant, leading to termination of the second pregnancy. During the third pregnancy (Second PND), while the mother was being cared for for breast cancer, the homozygous child was born without complications, and the mother underwent mastectomy following delivery. Over the following two years, the child has remained asymptomatic, and the mother has also remained healthy after the mastectomy. Successful PND of severe FVII deficiency was achieved through c.1A>G variant detection, with coordinated multidisciplinary care enabling favorable maternal and fetal outcomes despite concurrent breast cancer treatment.