Third trimester hydrops fetalis as the presentation leads to prenatal diagnosis of familial hemophagocytic lymphohistiocytosis

We first report a case of familial hemophagocytic lymphohistiocytosis (FHL) diagnosed in utero due to third trimester hydrops fetalis. A 28-year-old G1P0 woman had a normal nuchal translucency scan and 2 second trimester ultrasounds at 18 and 24 weeks. The third trimester ultrasound at 30 weeks showed mild polyhydramnios. The follow-up ultrasound at 32 weeks showed features of hydrops fetalis with pleural effusions, ascites, skin edema and polyhydramnios. Fetal blood sampling via cordocentesis showed a mild anemia (hemoglobin-100 g/L), thrombocytopenia (platelets-12×10 9 /L) and normal white blood cell counts (9.7×10 9 /L). Exome sequencing (ES) detected a novel homozygous pathogenic frameshift variant c.65del, p(Pro22ArgfsTer29) in PRF1 with biparental inheritance. Biallelic pathogenic variants in PRF1 are associated with FHL. This case indicates that third trimester hydrops fetalis with fetal anemia and thrombocytopenia are the diagnostic clue to the FHL. The use of prenatal ES can achieve a definite diagnosis.