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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 Molecular results revealed ten previously unpublished variants, one missense and nine predicted truncating variants (three frameshift, three nonsense and three splice site variants)., Conclusion: We report the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.)

Myhre syndrome (MS) is a rare genetic condition that presents with multiple genetic anomalies including cleft lip and palate and Eustachian tube dysfunction. These patients are at a high risk for airway scarring from intubation and mucosal inflammation. Hearing loss (conductive or mixed, of varying severity) is a common comorbidity in these patients, the exact etiology of which is still unclear. We present the cases of 2 unrelated children with MS who suffered progressive mixed hearing loss from fibrosis and obliteration of the middle ear spaces. Both patients had multiple sets of ear tubes that demonstrated early extrusion. The older patient underwent bone conduction implantation at age 11 which resulted in dramatic improvement of speech recognition and interactive skills. The other younger patient demonstrates a similar trajectory but has not yet undergone implantation. Otolaryngologists should take a cautious approach to surgery of the eardrum and middle ear to avoid unnecessary induction of fibrosis in this susceptible patient population. These cases highlight a newly described etiology for hearing loss and suggest a benefit to bone conduction implantation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.