Prenat Diagn

. 2024 Nov 14.

 doi: 10.1002/pd.6700. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/39542847/

Fetal Presentation of MYRF-Related Cardiac Urogenital Syndrome: An Emerging and Challenging Prenatal Diagnosis

Maud Favier ^1 2, Elise Brischoux-Boucher ¹, Louise C Pyle ³, Nicolas Mottet ⁴, Marion Auber-Lenoir ⁵, Julie Cattin ⁴, Eric Dahlen ⁶, Christelle Cabrol ¹, Francine Arbez-Gindre ⁷, Tania Attié-Bitach ^8 9, Odile Boute ¹⁰, Louise Devisme ¹⁰, Detlef Trost ¹¹, Aicha Boughalem ¹¹, David Chitayat ¹², Lev Prasov ^13 14, Odelia Chorin ¹⁵, Annick Rein-Rothschild ^15 16, Eran Kassif ^16 17, Tal Weissbach ^16 17, Laura Godfrey Hendon ¹⁸, Margaret P Adam ¹⁹, Chloé Quelin ^2 20, Sylvie Jaillard ²¹, Laura Mary ²¹, Sietse M Aukema ²², Malou Heijligers ²³, Christine de Die-Smulders ²³, Sander Stegmann ²³, Lauren Badalato ²⁴, Adi Ben-Yehuda ²⁵, Claire Beneteau ^2 26, Pierre-Louis Forey ²⁷, Paul Kuentz ^6 28, Juliette Piard ^1 28

Affiliations Expand

• PMID: 39542847
• DOI: 10.1002/pd.6700

Abstract

Purpose: MYRF-related cardiac-urogenital syndrome (MYRF-CUGS) is a rare condition associated with heterozygous MYRF variants. The description of MYRF-CUGS phenotype is mostly based on postnatal cases and 36 affected individuals have been published so far. We aim now to delineate the prenatal phenotype of MYRF-CUGS by reporting clinical data from fetuses and neonates with a pathogenic MYRF variant.

Methods: Detailed radiographic, pathological, clinical, and molecular data from 12 prenatal cases were collected through an international collaborative study. Adding the five fetuses previously published, we were able to study a cohort of 17 cases.

Results: Main ultrasound-accessible manifestations of MYRF-CUGS include congenital heart defects (13/17, 76%), congenital diaphragmatic hernia (10/17, 59%) and disorders of sexual differentiation in 46, XY fetuses (7/14; 50%). Postnatal examination and/or autopsy data highlighted additional birth defects and neurological findings with a large spectrum of severity. Molecular results revealed ten previously unpublished variants, one missense and nine predicted truncating variants (three frameshift, three nonsense and three splice site variants).

Conclusion: We report the first prenatal cohort of MYRF-CUGS, allowing us to further characterize the variable expressivity of this rare disorder in fetuses. Severe congenital anomalies with a poor prognosis are more frequent than previously described in postnatal cases. Our data suggest that MYRF-CUGS is characterized by a recurrent recognizable malformative association, accessible to prenatal diagnosis, with a significant intrafamilial phenotypic variability making genetic counseling challenging.

© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.