Katherine L Ludorf1, Renata H Benjamin1, Maria Luisa Navarro Sanchez1, Scott D McLean2, Hope Northrup3, Laura E Mitchell1, Peter H Langlois4, Mark A Canfield4, Angela E Scheuerle5, Daryl A Scott6, Christian P Schaaf7, Joseph W Ray8, Omobola Oluwafemi1, Han Chen9, Michael D Swartz10, Philip J Lupo11, A J Agopian12. 1. Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA. 2. Clinical Genetics Section, The Children's Hospital of San Antonio, San Antonio, TX, USA. 3. Department of Pediatrics, Division of Medical Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. 4. Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, TX, USA. 5. Department of Pediatrics, Division of Genetics and Metabolism, University of Texas Southwestern Medical Center, Dallas, TX, USA. 6. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA. 7. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA; Heidelberg University, Institute of Human Genetics, Heidelberg, Germany. 8. Department of Pediatrics, Division of Medical Genetics and Metabolism, University of Texas Medical Branch, Galveston, TX, USA. 9. Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA; Center for Precision Health, UTHealth School of Public Health and UTHealth School of Biomedical Informatics, Houston, TX, USA. 10. Department of Biostatistics and Data Science, UTHealth School of Public Health, Houston, TX, USA. 11. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA. 12. Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA. Electronic address: a.j.agopian@uth.tmc.edu.
Abstract
INTRODUCTION: Hypospadias, one of the most common male genital birth defects, occurs in 1 out of every 200 male births in the United States and is increasing in prevalence globally. OBJECTIVE: This study aimed to characterize the combinations of birth defects that co-occur with hypospadias more often than expected by chance, while accounting for the complex clustering patterns of congenital defects. STUDY DESIGN: We analyzed cases with hypospadias and at least one additional co-occurring defect from the Texas Birth Defect Registry born between 1999 and 2014. For each combination, we calculated adjusted observed-to-expected (O/E) ratios, using Co-Occurring Defect Analysis (CODA). RESULTS: Among 16,442 cases with hypospadias and without known syndromes, 2,084 (12.7%) had at least one additional defect. Many of the birth defect combinations within the highest adjusted O/E ratios included cardiac, musculoskeletal, and additional urogenital defects. For example, a top combination with an adjusted O/E of 139.0 included renal agenesis and dysgenesis, reduction defects of the upper limb, and other anomalies of upper limb (including shoulder girdle). High adjusted O/E ratios were also observed in combinations that included defects outside of the urogenital developmental field. For instance, the combination with the highest O/E ratio included buphthalmos, and congenital cataract and lens anomalies (adjusted O/E ratio: 192.9). Similar results were obtained when we restricted our analyses to cases with second- or third-degree hypospadias. DISCUSSION: Many combinations in the top results were expected (e.g., multiple urogenital defects); however, some combinations with seemingly unrelated patterns of defects may suggest the presence of some etiologic mechanisms yet to be identified. CONCLUSION: In summary, this study described patterns of co-occurring defect combinations with hypospadias that can inform further study and may provide insights for screening and diagnostic practices.
INTRODUCTION: Hypospadias, one of the most common male genital birth defects, occurs in 1 out of every 200 male births in the United States and is increasing in prevalence globally. OBJECTIVE: This study aimed to characterize the combinations of birth defects that co-occur with hypospadias more often than expected by chance, while accounting for the complex clustering patterns of congenital defects. STUDY DESIGN: We analyzed cases with hypospadias and at least one additional co-occurring defect from the Texas Birth Defect Registry born between 1999 and 2014. For each combination, we calculated adjusted observed-to-expected (O/E) ratios, using Co-Occurring Defect Analysis (CODA). RESULTS: Among 16,442 cases with hypospadias and without known syndromes, 2,084 (12.7%) had at least one additional defect. Many of the birth defect combinations within the highest adjusted O/E ratios included cardiac, musculoskeletal, and additional urogenital defects. For example, a top combination with an adjusted O/E of 139.0 included renal agenesis and dysgenesis, reduction defects of the upper limb, and other anomalies of upper limb (including shoulder girdle). High adjusted O/E ratios were also observed in combinations that included defects outside of the urogenital developmental field. For instance, the combination with the highest O/E ratio included buphthalmos, and congenital cataract and lens anomalies (adjusted O/E ratio: 192.9). Similar results were obtained when we restricted our analyses to cases with second- or third-degree hypospadias. DISCUSSION: Many combinations in the top results were expected (e.g., multiple urogenital defects); however, some combinations with seemingly unrelated patterns of defects may suggest the presence of some etiologic mechanisms yet to be identified. CONCLUSION: In summary, this study described patterns of co-occurring defect combinations with hypospadias that can inform further study and may provide insights for screening and diagnostic practices.
Authors: Xiao Yu; Natasha Nassar; Pierpaolo Mastroiacovo; Mark Canfield; Boris Groisman; Eva Bermejo-Sánchez; Annukka Ritvanen; Sonja Kiuru-Kuhlefelt; Adriana Benavides; Antonin Sipek; Anna Pierini; Fabrizio Bianchi; Karin Källén; Miriam Gatt; Margery Morgan; David Tucker; M Aaurora Canessa; Rosa Gajardo; Osvaldo M Mutchinick; Elena Szabova; Melinda Csáky-Szunyogh; Giovanna Tagliabue; Janet D Cragan; Wendy N Nembhard; Anke Rissmann; Dorit Goetz; Carol Bower; Gareth Baynam; R Brian Lowry; Juan A Leon; Wei Luo; Jocelyn Rouleau; Ignacio Zarante; Nicolas Fernandez; Emmanuelle Amar; Saeed Dastgiri; Paolo Contiero; Laura E Martínez-de-Villarreal; Barry Borman; J E H Bergman; Hermien E K de Walle; Charlotte A Hobbs; Amy E Nance; A J Agopian Journal: Eur Urol Date: 2019-07-09 Impact factor: 20.096
Authors: Sonja A Rasmussen; Richard S Olney; Lewis B Holmes; Angela E Lin; Kim M Keppler-Noreuil; Cynthia A Moore Journal: Birth Defects Res A Clin Mol Teratol Date: 2003-03
Authors: Melissa A Richard; Jenil Patel; Renata H Benjamin; Emine Bircan; Stephen J Canon; Lisa K Marengo; Mark A Canfield; A J Agopian; Philip J Lupo; Wendy N Nembhard Journal: JAMA Netw Open Date: 2022-07-01