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Optimizing genetic testing strategies for congenital anomalies in Iran

European Journal of Human Genetics (2024)Cite this article

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Congenital anomalies or birth defects are structural or functional abnormalities present at birth or in the developing fetus. They are estimated to affect 2–4% of infants worldwide. Examples include neural tube defects, brain malformations, congenital heart defects, urinary tract and kidney malformations, and limb malformations. Congenital anomalies are associated with increased risk of fetal demise and stillbirth, elevated mortality in liveborn infants, and increased risk of cancer [1]. Consequently, congenital anomalies represent a major issue for clinical genomics and public health. In this issue, Vaseghi et al. summarize the diagnostic evaluation of 168 individuals with congenital anomalies in a clinical laboratory in Iran and thereby provide valuable guidance to optimize clinical genetic testing decisions [2].

Congenital anomalies result from environmental and genetic factors. Many environmental factors have been identified including (1) folate deficiency and neural tube defects; (2) intrauterine infections like Toxoplasma, Rubella, Cytomegalovirus, Herpesvirus, and Zika; and (3) alcohol consumption and fetal alcohol spectrum disorders. Single gene disorders and genomic disorders including aneuploidy, microdeletions, and microduplications are the other major cause of congenital anomalies. Since the risk of recurrence of recessive disorders is high, rapid identification of an underlying genetic disorder is critical to inform reproductive choices. Furthermore, obtainment of a precision genetic diagnosis provides answers for families in difficult circumstances and increasingly permits genotype-directed prognostication and precision therapeutics including dietary modifications, small molecules, and RNA/DNA therapies.

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Fig. 1: Congenital anomalies affect 2–4% of infants worldwide.

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Funding

DGC was supported by the Child Neurologist Career Development Program (United States National Institute of Neurological Disorders and Stroke K12NS098482) and Muscular Dystrophy Association Development Grant (873841).

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Authors and Affiliations

  1. Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Daniel G. Calame

  2. Texas Children’s Hospital, Houston, TX, USA

    Daniel G. Calame

  3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Daniel G. Calame

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Correspondence to Daniel G. Calame.

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Calame, D.G. Optimizing genetic testing strategies for congenital anomalies in Iran. Eur J Hum Genet (2024). https://doi.org/10.1038/s41431-024-01578-y

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