Year: 2024
Type: article
Study design: Observational Study
Abstract: Background: Many patients with X-linked agammaglobulinemia (XLA) nowadays have reached adulthood, as well as their sisters, possibly carriers of a deleterious Bruton tyrosine kinase variant. Studies on motherhood outcomes in families with XLA are lacking. Objective: We sought to investigate adherence to carrier status screening, interest in preconception and prenatal genetic counseling, and reproductive decisions in relatives with XLA. Methods: In this multicenter, retrospective cohort study, we collected a 3-generation pedigree and data on mothers and sisters of patients with XLA, including carrier status and pregnancy outcome. Results: Data on 53 adults with XLA, 52 mothers, and 33 sisters were collected. All XLA sisters received genetic counseling. Forty percent of the sisters chose to undergo carrier status determination, and 60% of them chose invasive prenatal testing. The main reasons for the sisters to decide not to undergo genetic testing were their young age and the willingness to carry on with the pregnancy regardless of the outcome of the genetic test, followed by the willingness to postpone the decision at the time of pregnancy and the decision to not have children. Prenatal testing resulted in 5 XLA diagnoses, with 2 pregnancy terminations, 1 miscarriage, and 2 XLA live births. Three carriers refused prenatal testing and had 6 live births, including 3 XLA-affected sons. One sister was diagnosed as a carrier after the birth of an XLA-affected son. In total, 9 XLA diagnoses were made, including 6 live births. Conclusions: A number of XLA sister carriers decided to carry on with their pregnancy after receiving the diagnosis of an affected fetus or after refusing prenatal testing. We propose to initiate a more extensive collaborative study to verify the effect of genetic counseling on families with XLA in other cohorts from different countries.
Authors: Federica Pulvirenti, Cinzia Milito, Francesco Cinetto, Giulia Garzi, Germano Sardella, Giuseppe Spadaro, Francesca Lippi, Valentina Guarnieri, Bianca Laura Cinicola, Maria Carrabba, Daniele Guadagnolo, Giovanna Fabio, Baldassarre Martire, Caterina Cancrini, Giulia Lanzoni, Andrea Finocchi, Gigliola Di Matteo, Eva Pompilii, Simona Ferrari, Isabella Quinti
Institutions: Policlinico Umberto I, Sapienza University of Rome, University of Padua, Ca' Foncello Hospital, University of Naples Federico II, Meyer Children's Hospital, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Rome Tor Vergata, Bambino Gesù Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, GynePro Medical
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,000
Funder: Ministero della Salute
OpenAlex ID: W4405336496