Identification of Fowler syndrome (hydrocephaly-hydranencephaly proliferative vasculopathy) in a pregnancy following single euploid embryo transfer.

BACKGROUND

Genetic carrier screening is a useful tool for couples looking to understand the genetic risk profile of their offspring. However, this method is limited in identifying rare genetic variants.

CASE: A couple undergoing single euploid embryo transfer (SEET) following planned embryo banking was followed in this study. The patient was a 39-year-old nulliparous female with negative expanded carrier screening (ECS) which included 400 autosomal recessive and X-linked conditions. Her partner was a 39-year-old male with no pertinent past medical history. Clinical pregnancy was achieved following SEET. Unfortunately, the fetus demonstrated a constellation of neurologic malformations at 28 weeks gestation and the couple opted for termination. Amniocentesis was conducted at the time of labor induction revealing unremarkable chromosome analysis and microarray testing. Whole genome sequencing (WGS) noted paternal and maternal variants of the fetal leukemia virus subgroup C cellular receptor family, member 2 protein (FLVCR2). The paternal variant was classified as pathogenic, and the maternal variant was classified as a variant of uncertain significance by the lab. The presence of balletic FLVCR2 variants in the setting of neurologic anomalies was consistent with Fowler syndrome, a rare autosomal recessive condition.

CONCLUSION

This case highlights the inherent limitations of carrier screening in detecting rare genetic disease and marks the first documented case of Fowler syndrome following single euploid embryo transfer.