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Genetic testing is not a new concept in neonatology. Newborn metabolic screening is the largest utilization of universal genetic testing in medicine and has been used in neonatology since 1960. It was then that Dr. Robert Guthrie developed a blood test to screen infants for phenylketonuria. It is estimated that birth defects are detected in 3% to 6% of live births and that congenital malformations, deformations, and chromosomal abnormalities are the cause of approximately 20% of deaths before 1 year of age. Many genetic conditions present in the perinatal period. Understanding of the available technology and the ability to manage all the steps involved in genomic testing have become essential tools for nongenetic specialists, including neonatologists and pediatricians. The study of genetics and genomics overlaps in the DNA analysis of specific genes, with the majority of diseases having complex genetic signatures. Genomics is a relatively new field, arising with the completion of the Human Genome Project in 2003, which mapped over 3 billion nucleotides in the 23 human chromosomes. Genomic technology advances have had a major impact on the care of newborns, especially those who are critically ill. Consequently, genomic testing is used more frequently, and as a result, pediatric providers need to be knowledgeable about the wide variety of tools that are becoming available. Information in this chapter is applicable to the newborn screening and congenital abnormalities discussed in Chapters 16 and 93.


  1. Genetics versus genomics. These terms are commonly used interchangeably but are not strictly the same thing.

    1. Genetics refers to the study of a single or limited number of genes and their role in heredity.

    2. Genomics is a broader term and involves the study of the individual’s complete DNA sequence (genome). It can encompass the approximately 20,000 genes the genome contains and their interaction with each other and the environment in health and disease.

  2. Exons are parts of the DNA sequence that code for proteins, whereas introns are considered to be noncoding, intergenic regions, which are thought to contain regulatory elements.

  3. Exome is the total of all the exons (whole-exome sequencing [WES]).

  4. Genome is the complete DNA sequence, which includes the introns and exons (whole-genome sequencing [WGS]).

  5. Neome is a term coined to include approximately 1000 genes associated with diseases often presenting in the newborn period.

  6. Genetic sequence variation. The American College of Medical Genetics and Genomics (ACMG) has classified genetic variants on a 5-tier scale. Pathogenic, likely pathogenic, and variant of uncertain significance (VUS) are included in the clinical report; likely benign and benign variants are not usually included. Variant classification is based on available data, which is why it can change categories with time, going between pathogenic, likely pathogenic, benign, and so on.

    1. Pathogenic variant (previously called a mutation). A variant in a gene sequence known to cause a disorder or problem.

    2. Likely pathogenic variant. It is a variant in the gene strongly suspected to ...

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