Reproductive Implications of Consanguinity: Recurrent Hydrops and a Fetal Diagnosis of Lethal Gaucher Disease

Consanguinity is defined as a relationship with one recent ancestor in common. We present a Muslim couple with known consanguinity and their fetal outcomes over multiple pregnancies. This patient is a 28 yo G4P0300 who is married to her fourth cousin. Her first pregnancy was in Egypt during which a fetal demise was diagnosed at 21 weeks. Her second pregnancy ended in another fetal demise at 27 weeks and most organs were consistent with hydrops. Expanded carrier screening of both parents was negative. Her third pregnancy was complicated by hydropic changes at 21 weeks and fetal demise at 22 weeks. She consented to a trio whole exome sequence revealing a homozygous nonsense mutation c.1534A>T in the GBA gene. The mutation was found in the heterozygous state for each parent. Homozygosity for this mutation is associated with the perinatal lethal form of Gaucher disease, type 2. The patient was already 13 weeks pregnant when these results became available and she opted for a CVS procedure which confirmed that the fetus had not inherited any copies of the c.1534A>T mutation and was unaffected. While there is several case reports describing the Gaucher disease type 2, this case highlights the relevance of consanguinity. This case highlights the utility of whole exome sequencing in the setting of prenatal diagnosis and illustrates the significant limitations of expanded carrier screening when a genotyping panel is utilized with limited mutations per gene evaluated.