The new face of cystic fibrosis in the era of population genetic carrier screening

Miri Dotan; Hannah Blau; Amihood Singer; Patrick Stafler; Dario Prais; Malena Cohen-Cymberknoh; Joel Reiter; Ori Efrati; Adi Dagan; Lea Bentur; Michal Gur; Galit Livnat; Karin Yaacoby-Bianu; Micha Aviram; Inbal Golan Tripto; Ophir Bar-On; Reut Matar; Shani Hagit; Mira Malcov; Gheona Altarescu; Hanna Segev; Baruch Feldman; Eitan Kerem; Meir Mei-Zahav

doi:10.1016/j.jcf.2023.11.003

The new face of cystic fibrosis in the era of population genetic carrier screening

J Cyst Fibros. 2023 Nov 16:S1569-1993(23)01674-0. doi: 10.1016/j.jcf.2023.11.003. Online ahead of print.

Authors

Miri Dotan¹, Hannah Blau¹, Amihood Singer², Patrick Stafler¹, Dario Prais¹, Malena Cohen-Cymberknoh³, Joel Reiter³, Ori Efrati⁴, Adi Dagan⁴, Lea Bentur⁵, Michal Gur⁵, Galit Livnat⁶, Karin Yaacoby-Bianu⁶, Micha Aviram⁷, Inbal Golan Tripto⁷, Ophir Bar-On¹, Reut Matar⁸, Shani Hagit⁹, Mira Malcov¹⁰, Gheona Altarescu¹¹, Hanna Segev¹², Baruch Feldman¹³, Eitan Kerem³, Meir Mei-Zahav¹⁴

Affiliations

¹ Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
² Public Health Services, Ministry of Health, Jerusalem, Israel.
³ Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.
⁴ Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
⁵ Pediatric Pulmonary Institute and CF Center, Rambam Health Care Campus, Rappaport Children's Hospital, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
⁶ Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Pediatric Pulmonology Unit and CF center, Carmel Medical Center, Haifa, Israel.
⁷ Soroka University Medical Center, Pediatric Pulmonary Unit, Ben Gurion University, Beer Sheva, Israel.
⁸ Raphael Recanati Genetic Institute, Rabin Medical Center, Petach Tikva, Israel.
⁹ Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat-Gan, Israel.
¹⁰ Wolfe PGD-Stem Cell Laboratory, Racine IVF Unit, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
¹¹ Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
¹² Medical Genetics Institute, Rambam Health Care Campus, Haifa, Israel.
¹³ PGD Program and Laboratory, Assuta Medical Center, Tel Aviv, Israel.
¹⁴ Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: meir_zahav@clalit.org.il.

PMID: 37980178
DOI: 10.1016/j.jcf.2023.11.003

Abstract

Background: Population genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features.

Methods: This was a retrospective national study. Demographic and clinical characteristics of children with CF born in Israel between 2008 and 2018 were obtained from the national CF registry and from patients' medical records. Data on CF births, preimplantation genetic testing (PGT), pregnancy termination and de-identified data from the PGCS program were collected.

Results: CF births per 100,000 live births decreased from 8.29 in 2008 to 0.54 in 2018 (IRR = 0.84, p < 0.001). The CF pregnancy termination rate did not change (IRR = 1, p= 0.9) while the CF-related PGT rate increased markedly (IRR = 1.33, p < 0.001). One hundred and two children were born with CF between 2008 and 2018 with a median age at diagnosis of 4.8 months, range 0-111 months. Unlike the generally high uptake nationally, 65/102 had not performed PGCS. Even if all had utilized PGCS, only 51 would have been detected by the existing genetic screening panel. Clinically, 34 % of children were pancreatic sufficient compared to 23 % before 2008 (p = 0.04).

Conclusions: Since institution of a nationwide PGCS program, the birth of children with CF decreased markedly. Residual function variants and pancreatic sufficiency were more common. A broader genetic screening panel and increased PGCS utilization may further decrease the birth of children with CF.

Keywords: Antenatal screening; Cystic fibrosis; Population carrier screening; Pre-implantation genetic diagnosis.