Identifying Environmental Risk Factors and Gene-environment Interactions in Holoprosencephaly

Overview

Journal Birth Defects Res

Specialties Reproductive Medicine
Toxicology

Date 2020 Oct 28

PMID 33111505

Citations 10

Authors

Yonit A Addissie

Angela Troia

Zoe C Wong

Joshua L Everson

Beth A Kozel

Maximilian Muenke

Robert J Lipinski

Kristen M C Malecki

Paul Kruszka

Affiliations

Soon will be listed here.

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.

Citing Articles

Use of an Orthodontic and Otolaryngological Approach in an Infant with Holoprosencephaly.

Galeotti A, De Vincentiis G, Sitzia E, Marzo G, Maldonato W, Bompiani G Children (Basel). 2024; 11(5).

PMID: 38790549 PMC: 11119934. DOI: 10.3390/children11050554.

Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams-Beuren Syndrome.

Liu D, Billington Jr C, Raja N, Wong Z, Levin M, Resch W J Am Heart Assoc. 2024; 13(3):e031377.

PMID: 38293922 PMC: 11056152. DOI: 10.1161/JAHA.123.031377.

Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management.

Malta M, AlMutiri R, Martin C, Srour M Children (Basel). 2023; 10(4).

PMID: 37189898 PMC: 10137117. DOI: 10.3390/children10040647.

Birth defects data from hospital-based birth defect surveillance in Guilin, China, 2018-2020.

Yang X, Zeng J, Gu Y, Fang Y, Wei C, Tan S Front Public Health. 2022; 10:961613.

PMID: 36091541 PMC: 9449144. DOI: 10.3389/fpubh.2022.961613.

Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.

Bando H, Brinkmeier M, Castinetti F, Fang Q, Lee M, Saveanu A Hum Mol Genet. 2022; 32(3):367-385.

PMID: 35951005 PMC: 9851746. DOI: 10.1093/hmg/ddac192.

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