What is the Role of Genetics in the Development of Birth Defects?

What is the Role of Genetics in the Development of Birth Defects?

An overview of genetic birth defects and how genetic testing for embryos can help parents.

Written by Maria Katz, MS, CGC,
Reviewed by Xiaoli Du, PhD, FACMG, DABMGG, CGC,CGMBS

Dr. Du is an American Board of Medical Genetics and Genomics (ABMGG) certified geneticist. With a passion for precision medicine, she leverages cutting-edge molecular genetics and cytogenetics technology to improve outcomes for individuals affected by genetic conditions. Dr. Du has nine years of clinical genetic diagnosis experience in both the public and private sectors.

Birth defects are a complex group of conditions that can significantly impact the lives of affected individuals and their families. While various factors can contribute to the occurrence of birth defects, genetics plays a crucial role in their development.
During embryonic development, various genes are activated and used to help cells grow and become different tissues and organs in the body. However, when certain genes fail to function correctly, it can disrupt normal development and lead to birth defects. One example is skeletal dysplasias, a group of genetic disorders affecting bone growth and development. For example, mutations in genes responsible for the production of collagen, such as COL1A1 and COL1A2, can lead to Osteogenesis Imperfecta, a condition characterized by brittle bones and frequent fractures. In this case, the non-working genes result in abnormal collagen production, compromising the structural integrity of bones and impacting their ability to function properly. About 17% of birth defects happen because of problems with a single gene.

Abnormal chromosomes can also have a profound impact on embryonic development and can contribute to the occurrence of birth defects. Chromosomes carry a large amount of genetic information, and if there are any changes in the structure or number of chromosomes, it can disrupt how genes work. One well-known example is Down syndrome, which happens when there is an extra copy of chromosome 21. About 50% of babies with Down syndrome have a heart defect. Changes in chromosomes can affect the growth and development of organs. Approximately 10% of birth defects arise due to chromosomal differences.

What causes abnormal genes/chromosomes? 
Age related risks 

As parents age, there is an increased risk of birth defects in their offspring. Advancing paternal age has been linked to a higher likelihood of new mutations (known as de novo mutations) occurring in sperm. These mutations can contribute to genetic conditions like Osteogenesis Imperfecta, which was mentioned earlier. Likewise, in women, as they get older, their eggs may be more prone to chromosomal differences, such as Down syndrome. The cumulative effect of age-related genetic changes in reproductive cells emphasizes the significance of considering parental age when discussing the risk of birth defects4.

Spontaneous (de novo) genetic birth defects

Regardless of parental age, any pregnancy has a chance of a spontaneous genetic abnormality occurring during conception. These mutations, referred to as de novo mutations, are not inherited from either parent but arise spontaneously in the developing embryo5

Inherited genetic birth defects

Some birth defects result from inheriting abnormal genes from one or both parents. Examples of such conditions include Smith-Lemli-Opitz Syndrome, Spondylocostal dysostosis, and Infantile Polycystic Kidney Disease. Understanding your family history and identifying potential genetic risk factors are crucial in assessing the likelihood of passing on these conditions to future generations. 

Chromosomal conditions

Chromosome conditions, including Down syndrome (trisomy 21), primarily arise by chance during the formation of reproductive cells. Errors in chromosome division can result in an abnormal number of chromosomes in the developing embryo. The likelihood of chromosomal differences increases with advancing maternal age. While most chromosomal conditions occur sporadically, there are instances where unaffected parents can pass on these conditions to their children. However, such inherited cases are relatively rare compared to the spontaneous occurrence of chromosome conditions.

Can I test my embryo for birth defects? 

While it is not possible to test an embryo for birth defects, it is possible to screen an embryo for known chromosomal conditions and genes that can disrupt fetal development and potentially lead to birth defects.

In the case of a known genetic condition within your family, Orchid offers the option to directly screen your embryos. However, it is important to note that certain chromosomal and genetic abnormalities can arise spontaneously in an embryo, regardless of personal or family history. Orchid's screening processes encompass a range of conditions associated with birth defects, including:

  • Chromosomal conditions such as Down Syndrome
  • Small microdeletion and microduplications that can cause heart, renal, skeletal and craniofacial birth defects. 
  • Genes associated with skeletal dysplasias, which impact the growth and development of bones and cartilage. It is estimated that approximately 5% of all birth defects are classified as skeletal dysplasias.
  • Genes associated with heart defects. For instance, Noonan Syndrome (NS) is a prevalent single gene disorder known to be a significant cause of congenital heart defects, with a high incidence rate ranging from 50% to 80%. A genetic cause can be found in approximately 20-30% of individuals with a cardiac defect.
  • Genes associated with metabolic conditions. Genetic metabolic conditions can have a profound impact on fetal development, increasing the risk of birth defects. One example of a genetic metabolic condition that Orchid screen for is Desmosterolosis. This condition is characterized by multiple congenital anomalies, which result from a disruption in an enzyme involved in the cholesterol biosynthesis pathway.

Genetics plays a crucial role in the development of birth defects. Abnormal genes and chromosomes can lead to disruptions in the intricate processes of embryonic development, potentially resulting in various congenital anomalies. Orchid’s embryo screening has become an invaluable tool in identifying genetic abnormalities prior to pregnancy. Only Orchid offers the option for screening embryos for 900+ genes and chromosomal abnormalities that have been known to lead to birth defects. This screening technique provides valuable insights into potential birth defects and enables informed decision-making for parents and healthcare providers. 


1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteogenesis Imperfecta. Retrieved from:https://www.niams.nih.gov/health-topics/osteogenesis-imperfecta
2. Nelson, K., & Holmes, L. B. (1989). Malformations due to presumed spontaneous mutations in newborn infants. The New England journal of medicine, 320(1), 19–23.
3. National Institute of Health. What conditions or disorders are commonly associated with Down syndrome? Retrieved from:
4. Toriello, H. V., Meck, J. M., & Professional Practice and Guidelines Committee (2008). Statement on guidance for genetic counseling in advanced paternal age. Genetics in medicine : official journal of the American College of Medical Genetics, 10(6), 457–460.
5. Acuna-Hidalgo, R., Veltman, J. A., & Hoischen, A. (2016). New insights into the generation and role of de novo mutations in health and disease. Genome biology, 17(1), 241.
6. Goldmuntz, E., Paluru, P., Glessner, J., Hakonarson, H., Biegel, J. A., White, P. S., Gai, X., & Shaikh, T. H. (2011). Microdeletions and microduplications in patients with congenital heart disease and multiple congenital anomalies. Congenital heart disease, 6(6), 592–602.
7. Krakow D. (2015). Skeletal dysplasias. Clinics in perinatology, 42(2), 301–viii.
8. Yasuhara, J., & Garg, V. (2021). Genetics of congenital heart disease: a narrative review of recent advances and clinical implications. Translational pediatrics, 10(9), 2366–2386.
9. Medline Plus. Metabolic Disorders. Retrieved from:
10. Marouane, A., Olde Keizer, R. A. C. M., Frederix, G. W. J., Vissers, L. E. L. M., de Boode, W. P., & van Zelst-Stams, W. A. G. (2022). Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study. European journal of pediatrics, 181(1), 359–367.

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