Jeremy M Schraw1,2, Renata H Benjamin3, Daryl A Scott4,5, Brian P Brooks6, Robert B Hufnagel6, Scott D McLean7, Hope Northrup8, Peter H Langlois9,10, Mark A Canfield10, Angela E Scheuerle11, Christian P Schaaf4,12,13, Joseph W Ray14, Han Chen3,15, Michael D Swartz16, Laura E Mitchell3, A J Agopian3, Philip J Lupo1,2. 1. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas. 2. Department of Pediatrics, Center for Epidemiology and Population Health, Baylor College of Medicine, Houston, Texas. 3. Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas. 4. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. 5. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas. 6. Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland. 7. Clinical Genetics Section, The Children's Hospital of San Antonio, San Antonio, Texas. 8. Department of Pediatrics, Division of Medical Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas. 9. Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Austin, TX. 10. Texas Department of State Health Services, Birth Defects Epidemiology and Surveillance Branch, Austin, Texas. 11. Department of Pediatrics, Division of Genetics and Metabolism, University of Texas Southwestern Medical Center, Dallas, Texas. 12. Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas. 13. Institute of Human Genetics, Heidelberg University, Heidelberg, Germany. 14. Department of Pediatrics, Division of Medical Genetics and Metabolism, University of Texas Medical Branch, Galveston, Texas. 15. Center for Precision Health, UTHealth School of Biomedical Informatics, Houston, Texas. 16. Department of Biostatistics and Data Science, UTHealth School of Public Health, Houston, Texas.
Abstract
PURPOSE: Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defect patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate. METHODS: This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two - through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases. RESULTS: We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects. CONCLUSION: Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defect registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.
PURPOSE: Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defect patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate. METHODS: This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two - through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases. RESULTS: We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects. CONCLUSION: Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defect registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.
Authors: Renata H Benjamin; Xiao Yu; Maria Luisa Navarro Sanchez; Han Chen; Laura E Mitchell; Peter H Langlois; Mark A Canfield; Michael D Swartz; Angela E Scheuerle; Daryl A Scott; Hope Northrup; Christian P Schaaf; Joseph W Ray; Scott D McLean; Philip J Lupo; A J Agopian Journal: Birth Defects Res Date: 2019-07-16 Impact factor: 2.344
Authors: Tiffany M Chambers; A J Agopian; Richard A Lewis; Peter H Langlois; Heather E Danysh; Kari A Weber; Gary M Shaw; Laura E Mitchell; Philip J Lupo Journal: Am J Med Genet A Date: 2018-08-02 Impact factor: 2.802
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Authors: Benjamin S Harris; Katherine C Bishop; Hanna R Kemeny; Jennifer S Walker; Eleanor Rhee; Jeffrey A Kuller Journal: Obstet Gynecol Surv Date: 2017-02 Impact factor: 2.347
Authors: Laurel Cavallo; Erin M Kovar; Amal Aqul; Lucille McLoughlin; Naveen K Mittal; Norberto Rodriguez-Baez; Benjamin L Shneider; Robert J Zwiener; Tiffany M Chambers; Peter H Langlois; Mark A Canfield; A J Agopian; Philip J Lupo; Sanjiv Harpavat Journal: J Pediatr Date: 2022-03-30 Impact factor: 6.314