Citation:

Stadler, H., C. Peters, R. Sturm, L. Baker, C. Best, V. Byrd, F. Geller, D. Hoshizaki, T. Knudsen, J. Norton, R. Romao, AND M. Cohn. Challenges and Opportunities for Translational Research on Congenital Anomalies of External Genitalia:Summary of an NIDDK/AUA Workshop. Journal of Pediatric Urology. Elsevier B.V., Amsterdam, Netherlands, 16(6):791-804, (2020). https://doi.org/10.1016/j.jpurol.2020.09.012

Impact/Purpose:

Congenital anomalies of the external genitalia (CAEG)1 are a prevalent and serious public health concern with lifelong impacts on urinary function, sexual health, fertility, tumor development, and the psychosocial well-being of affected individuals. While surgery is required to treat many of these conditions, complications are frequent and high quality epidemiological data reflecting long-term outcomes in adulthood are limited. Improving treatments and realizing the possibility of preventing CAEG will require the coordinated efforts of different research disciplines to fully understand the different etiologies of these common conditions, the subsequent variation in clinical phenotypes, and the best practices for long term surgical success. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the American Urological Association (AUA) convened researchers from a range of disciplines, including pediatric urology, developmental biology, genetics & genomics, computational systems biology, toxicology, endocrinology, and epidemiology to discuss the best way forward to address this public health concern. The manuscript is targeted to the Journal of Pediatric Urology.

Description:

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.

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