Favier Maud, Brischoux-Boucher Elise, Pyle Louise C, Mottet Nicolas, Auber-Lenoir Marion, Cattin Julie, Dahlen Eric, Cabrol Christelle, Arbez-Gindre Francine, Attié-Bitach Tania, Boute Odile, Devisme Louise, Trost Detlef, Boughalem Aicha, Chitayat David, Prasov Lev, Chorin Odelia, Rein-Rothschild Annick, Kassif Eran, Weissbach Tal, Hendon Laura Godfrey, Adam Margaret P, Quelin Chloé, Jaillard Sylvie, Mary Laura, Aukema Sietse M, Heijligers Malou, de Die-Smulders Christine, Stegmann Sander, Badalato Lauren, Ben-Yehuda Adi, Beneteau Claire, Forey Pierre-Louis, Kuentz Paul, Piard Juliette
Centre de Génétique Humaine, Centre Hospitalier Universitaire de Besançon, Université de Franche-Comté, Besançon, France.
SoFFoet - Société Française de Foetopathologie, Paris, France.
Prenat Diagn. 2024 Dec;44(13):1647-1658. doi: 10.1002/pd.6700. Epub 2024 Nov 14.
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.
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.
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 Molecular results revealed ten previously unpublished variants, one missense and nine predicted truncating variants (three frameshift, three nonsense and three splice site variants).
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.
MYRF相关的心肾泌尿综合征（MYRF-CUGS）是一种与MYRF杂合变异相关的罕见疾病。MYRF-CUGS表型的描述大多基于出生后病例，迄今为止已发表了36例受影响个体的报告。我们现在旨在通过报告具有致病性MYRF变异的胎儿和新生儿的临床数据来描述MYRF-CUGS的产前表型。
通过一项国际合作研究收集了12例产前病例的详细影像学、病理学、临床和分子数据。加上之前发表的5例胎儿，我们能够研究一组17例病例。
MYRF-CUGS主要的超声可及表现包括先天性心脏缺陷（13/17，76%）、先天性膈疝（10/17，59%）以及46，XY胎儿的性分化障碍（7/14；50%）。出生后检查和/或尸检数据突出了其他出生缺陷和具有广泛严重程度的神经学发现。分子结果揭示了10个先前未发表的变异，1个错义变异和9个预测的截短变异（3个移码变异、3个无义变异和3个剪接位点变异）。
我们报告了首个MYRF-CUGS产前队列，使我们能够进一步描述这种罕见疾病在胎儿中的可变表达性。预后不良的严重先天性异常比之前出生后病例中描述的更为常见。我们的数据表明，MYRF-CUGS的特征是一种可重复识别的畸形关联，可进行产前诊断，家族内表型变异显著，这使得遗传咨询具有挑战性。
