Yonit A Addissie1, Angela Troia2, Zoe C Wong2, Joshua L Everson3,4, Beth A Kozel2, Maximilian Muenke1, Robert J Lipinski3,4, Kristen M C Malecki4,5, Paul Kruszka1. 1. Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland, USA. 2. Cardiovascular & Pulmonary Branch, National Heart, Lung, and Blood Institute, The National Institutes of Health, Bethesda, Maryland, USA. 3. Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA. 4. Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin, USA. 5. Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Abstract
BACKGROUND: Holoprosencephaly is the most common malformation of the forebrain (1 in 250 embryos) with severe consequences for fetal and child development. This study evaluates nongenetic factors associated with holoprosencephaly risk, severity, and gene-environment interactions. METHODS: For this retrospective case control study, we developed an online questionnaire focusing on exposures to common and rare toxins/toxicants before and during pregnancy, nutritional factors, maternal health history, and demographic factors. Patients with holoprosencephaly were primarily ascertained from our ongoing genetic and clinical studies of holoprosencephaly. Controls included children with Williams-Beuren syndrome (WBS) ascertained through online advertisements in a WBD support group and fliers. RESULTS: Difference in odds of exposures between cases and controls as well as within cases with varying holoprosencephaly severity were studied. Cases included children born with holoprosencephaly (n = 92) and the control group consisted of children with WBS (n = 56). Pregnancy associated risk associated with holoprosencephaly included maternal pregestational diabetes (9.2% of cases and 0 controls, p = .02), higher alcohol consumption (adjusted odds ratio [aOR], 1.73; 95% CI, 0.88-15.71), and exposure to consumer products such as aerosols or sprays including hair sprays (aOR, 2.46; 95% CI, 0.89-7.19). Significant gene-environment interactions were identified including for consumption of cheese (p < .05) and espresso drinks (p = .03). CONCLUSION: The study identifies modifiable risk factors and gene-environment interactions that should be considered in future prevention of holoprosencephaly. Studies with larger HPE cohorts will be needed to confirm these findings.
BACKGROUND: Holoprosencephaly is the most common malformation of the forebrain (1 in 250 embryos) with severe consequences for fetal and child development. This study evaluates nongenetic factors associated with holoprosencephaly risk, severity, and gene-environment interactions. METHODS: For this retrospective case control study, we developed an online questionnaire focusing on exposures to common and rare toxins/toxicants before and during pregnancy, nutritional factors, maternal health history, and demographic factors. Patients with holoprosencephaly were primarily ascertained from our ongoing genetic and clinical studies of holoprosencephaly. Controls included children with Williams-Beuren syndrome (WBS) ascertained through online advertisements in a WBD support group and fliers. RESULTS: Difference in odds of exposures between cases and controls as well as within cases with varying holoprosencephaly severity were studied. Cases included children born with holoprosencephaly (n = 92) and the control group consisted of children with WBS (n = 56). Pregnancy associated risk associated with holoprosencephaly included maternal pregestational diabetes (9.2% of cases and 0 controls, p = .02), higher alcohol consumption (adjusted odds ratio [aOR], 1.73; 95% CI, 0.88-15.71), and exposure to consumer products such as aerosols or sprays including hair sprays (aOR, 2.46; 95% CI, 0.89-7.19). Significant gene-environment interactions were identified including for consumption of cheese (p < .05) and espresso drinks (p = .03). CONCLUSION: The study identifies modifiable risk factors and gene-environment interactions that should be considered in future prevention of holoprosencephaly. Studies with larger HPE cohorts will be needed to confirm these findings.
Authors: Paul Kruszka; Seth I Berger; Karin Weiss; Joshua L Everson; Ariel F Martinez; Sungkook Hong; Kwame Anyane-Yeboa; Robert J Lipinski; Maximilian Muenke Journal: Am J Hum Genet Date: 2019-04-18 Impact factor: 11.025
Authors: April D Summers; Jennita Reefhuis; Joanna Taliano; Sonja A Rasmussen Journal: Am J Med Genet C Semin Med Genet Date: 2018-05-15 Impact factor: 3.908
Authors: Kristen M C Malecki; Maria Nikodemova; Amy A Schultz; Tamara J LeCaire; Andrew J Bersch; Lisa Cadmus-Bertram; Corinne D Engelman; Erika Hagen; Mari Palta; Ajay K Sethi; Matt C Walsh; F Javier Nieto; Paul E Peppard Journal: medRxiv Date: 2021-04-07
Authors: Kristen M C Malecki; Maria Nikodemova; Amy A Schultz; Tamara J LeCaire; Andrew J Bersch; Lisa Cadmus-Bertram; Corinne D Engelman; Erika Hagen; Laura McCulley; Mari Palta; Allison Rodriguez; Ajay K Sethi; Matt C Walsh; F Javier Nieto; Paul E Peppard Journal: Front Public Health Date: 2022-03-31