What Parents Need to Know About Genetic Testing

Pediatricians may recommend a genetics consult or genetic testing for a child.

This may be recommended if a child experiences developmental disabilities or delay of motor, speech, or cognitive function. Children with structural birth defects, either single-organ defects or multiple major and/or minor anomalies that are present in different organs, may also seek genetic testing. Children who have chronic functional problems in 1 or more organs, such as problems with vision or hearing, neuromuscular problems affecting movement and activity, seizures, chronic behavioral or mood problems, immune problems with frequent illness, hormone problems, poor growth, chronic digestive problems, or heart rhythm problems, among others, may also benefit from genetic testing. A family history of genetic disease may be a sufficient reason to consider genetic testing.

Most genetic problems are due to mutations in 1 or both copies of a nuclear gene, with nearly 7000 known single-gene disorders now recognized among more than 20 000 gene pairs.

• Autosomal recessive diseases result from both copies of a given gene having a disease-causing mutation (pathogenic variant). Parents are each asymptomatic carriers for a single mutation (which may be the same or different) and together have a 1 in 4 (25%) likelihood of having each pregnancy inherit both mutations and be affected by the disease.

• Autosomal dominant diseases result from a disease-causing mutation in 1 copy of a given gene, which may have occurred new in the affected child or be inherited from a parent with similar or sometimes less severe symptoms so that their own disease was not recognized.

• X-linked diseases result from a disease-causing mutation in a gene on the X chromosome, which typically appears more severely in boys. These can occur new in the affected child or be inherited from an asymptomatic mother.

• Some genetic problems that may involve dysfunction of nearly any body system result from mutations in the mitochondrial DNA, which has 37 genes that are inherited from the mother through the oocyte. Mitochondrial DNA disease can be inherited from a symptomatic or healthy mother or occur new in the affected child (both boys and girls).

Families should undergo careful counseling before pursuing genetic testing with an experienced health care professional. As genetic testing results are often complex, families should discuss these with a clinical genetics professional to provide accurate test interpretation. Test results need to be considered in the context of each child’s unique medical problems, avoiding false reassurance or incorrect conclusions, and used to recommend appropriate next steps.

A prolonged and sometimes complicated search for a diagnosis can effectively end when the specific gene cause(s) is identified for a child’s medical problems. Correctly understanding the cause of a child’s medical problems can remove the sense of blame or guilt often felt by the child or parents, who may wonder what factors contributed to their cause. Identifying the underlying causal genetic disorder can lead to improved management or targeted therapies by your child’s health care team, implementation of effective behavioral or education strategies, insurance coverage, support networks, and screening for other problems that may be prevented or treated. Having knowledge of the precise gene mutation causing a child’s problems can empower future reproductive choices of the child, parents, and extended family members and can potentially optimize broader family health.

Published Online: February 25, 2019. doi:10.1001/jamapediatrics.2019.0005

Conflict of Interest Disclosures: Dr Falk reports personal fees from Mitobridge, grants and personal fees from NeuroVive, grants from Stealth BioTherapeutics, nonfinancial support from United Mitochondrial Disease Foundation outside the submitted work, and an issued patent (#61/898,171). No other disclosures were reported.