Is a definite genetic diagnosis all we need to manage patients with Inborn Error of Immunity prenatally and during childbearing? Running title: Prenatal and Childbearing Considerations

Abstract

Abstract Background: Patients with inborn errors of immunity (IEI) who want to have children face concerns about the impact of their condition on fertility, pregnancy, and disease inheritance. In tribal cultures with consanguineous marriages, prenatal genetic counseling is critical. Case presentation: 10 families with genetically confirmed IEI were reported: An architect with an autosomal dominant STAT-1 gain of function who had planned preimplantation genetic diagnosis (PGD) to prevent disease transmission. However, she unexpectedly became pregnant and underwent prenatal diagnosis (PND) at 12 weeks. Despite the diagnosis, her husband refused to allow her to abort the affected child. Another case involved a consanguineous family who lost their first child to leukocyte adhesion deficiency type 1 (LAD1). The second child was also affected. Despite the availability of PND during the second pregnancy, the father refused the procedure. In another instance, a first cousin couple had two children with Bruton disease. Despite being informed about the disease, the mother refused to abort her second child. Likewise, a consanguineous couple with two children affected by Ataxia Telangiectasia opted for a donated oocyte for their third child, resulting in a healthy child. Recurrent pregnancy loss (RPL) was observed in a mother who was later diagnosed with ZAP70 deficiency. In another case, a mother with a child affected by Wiskott Aldrich Syndrome (WAS) underwent in vitro fertilization (IVF) without sex selection, resulting in a healthy boy after PND was performed during pregnancy. In a family with multiple cases of WAS, another child was mistakenly diagnosed with anaplastic anemia. A case of LAD1 resulted in the parents' divorce, with the father denying the child's condition and impeding necessary bone marrow transplantation. In a non-consanguineous couple, the father was diagnosed with TACHI deficiency and Hypogammaglobulinemia. PND revealed that the mother and child had the same heterozygote gene, leading the mother to decide against continuing the pregnancy. Conclusion: Genetic diagnosis alone is not enough for optimal prenatal care in immune dysregulation disorders. Factors like patient awareness, social beliefs, ethics, and economic considerations impact pregnancy decisions. Clinical immunologists must consider these factors and provide guidance for better outcomes.