Meeting report on the NIDDK/AUA Workshop on Congenital Anomalies of External Genitalia: challenges and opportunities for translational research. Issue 6 (December 2020)

• Record Type: Journal Article
• Authors: Stadler, H. Scott; Peters, Craig A.; Sturm, Renea M.; Baker, Linda A.; Best, Carolyn J.M.; Bird, Victoria Y.; Geller, Frank; Hoshizaki, Deborah K.; Knudsen, Thomas B.; Norton, Jenna M.; Romao, Rodrigo L.P.; Cohn, Martin J.
• Is Part Of: Journal of pediatric urology. Volume 16:Issue 6(2020)
• Page Start: 791
• Page End: 804
• Publication Date: 2020-12
• Subjects: Hypospadias -- Genitourinary development -- Chordee -- Epispadias -- Genetics -- Endocrine disruption -- Penis -- Urethra; ABM agent-based models -- AOP adverse outcome pathway -- AUA American Urological Association -- BMP bone morphogenic protein -- CAEG Congenital anomalies of the external genitalia -- DNA deoxyribonucleic acid -- EDC endocrine disrupting chemicals -- EGF epidermal growth factor -- EFNB ephrin B -- EHR electronic health record -- EYA1 EYA transcriptional coactivator and phosphatase 1 -- FGF fibroblast growth factor -- GWAS genome-wide association study -- HGF Hepatocyte growth factor -- ICD-10 International Classification of Diseases, 10th Revision -- IGF Insulin-like growth factor -- IRX Iroquois-class homeodomain -- RNA ribonucleic acid -- SHH Sonic hedgehog -- SNP single nucleotide polymorphism -- VP phenotypic variance -- VG genomic variance -- VE environmental variance -- VGE genome–environmental interaction variance -- WNT Wingless-INT; Pediatric urology -- Periodicals; Urologic Diseases -- Periodicals; Urogenital Diseases -- Periodicals; Urologic Surgical Procedures -- Periodicals; Child; Infant; Urologie pédiatrique -- Périodiques; Appareil urinaire -- Maladies -- Périodiques; Pédiatrie; Urologie; Pediatric urology; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); Electronic journals; Periodicals; Electronic journals; 618.926
• DOI: 10.1016/j.jpurol.2020.09.012
• Languages: English
• ISSNs: 1477-5131

Abstract

Summary: Congenital anomalies of the external genitalia (CAEG) are a prevalent and serious public health concern with lifelong impacts on the urinary function, sexual health, fertility, tumor development, and psychosocial wellbeing of affected individuals. Complications of treatment are frequent, and data reflecting long-term outcomes in adulthood are limited. To identify a path forward to improve treatments and realize the possibility of preventing CAEG, the National Institute of Diabetes and Digestive and Kidney Diseases and the American Urological Association convened researchers from a range of disciplines to coordinate research efforts to fully understand the different etiologies of these common conditions, subsequent variation in clinical phenotypes, and best practices for long term surgical success. Meeting participants concluded that a central data hub for clinical evaluations, including collection of DNA samples from patients and their parents, and short interviews to determine familial penetrance (small pedigrees), would accelerate research in this field. Such a centralized datahub will advance efforts to develop detailed multi-dimensional phenotyping and will enable access to genome sequence analyses and associated metadata to define the genetic bases for these conditions. Inclusion of tissue samples and integration of clinical studies with basic research using human cells and animal models will advance efforts to identify the developmental mechanisms that are disrupted during development and will add cellular and molecular granularity to phenotyping CAEG. While the discussion focuses heavily on hypospadias, this can be seen as a potential template for other conditions in the realm of CAEG, including cryptorchidism or the exstrophy–epispadias complex. Taken together with long-term clinical follow-up, these data could inform surgical choices and improve likelihood for long-term success.