State of the Art Pediatrics: Guidelines for Genetic Testing

Evolving guidelines for genetic testing bring challenges to primary care providers, who are increasingly being called on to diagnose and evaluate children with neurodevelopmental disorders. While many of these children could benefit from genetic testing, the number of available tests being offered can feel overwhelming. The Children’s Mercy Clinical Genetics and Genomics Laboratory has several laboratory genetic counselors to assist community providers in obtaining the right testing for their patients.

What is the best first-line test?

The current American Academy of Pediatrics (AAP) recommendation for first-line genetic testing in a child with developmental delay or autism is exome or genome sequencing (ES/GS).¹ ES/GS offers an increased diagnostic yield over previous approaches such as karyotype or microarray because it can detect both sequence level and copy number variants. At Children’s Mercy, we offer a symptom-driven exome analysis, which means that we investigate variants in genes associated with a child’s symptoms, a method that decreases the likelihood of unrelated findings. When available, we include samples from parents at no additional charge, which improves the diagnostic yield and aids in interpretation.

No genetic test can detect every disorder, so if the initial testing is nondiagnostic, additional tests may be considered. These tests are typically targeted toward a single disorder and require different laboratory techniques such as analysis for repeat expansions or methylation disorders.

If there are family members known to have a genetic diagnosis, targeted (familial variant) testing is more cost effective and efficient.

How do I order testing?

The Children’s Mercy Provider Test Catalog (https://childrensmercylab.testcatalog.org) has a list of genetic tests and requisitions for ordering testing. Most insurance providers require preauthorization for genetic testing, so it’s important to have the authorization in place before sending the patient to the lab for sample collection. When ordering a symptom-driven exome with parental samples, please order “Parent NGS” or “DNA isolation” on the parents separately.

The ideal sample type for most genetic testing is blood, but many tests can be performed on a buccal/saliva swab as well. The Children’s Mercy outpatient labs have these swabs available; please specify “buccal/saliva swab” in the order.

Insurance challenges

Unfortunately, delays between the publication of professional guidelines related to laboratory testing recommendations and payor coverage for that testing are common. In those situations, in order to get a more comprehensive test like exome covered, a provider and family might need to break away from the AAP guidelines for testing and pursue a microarray first. In addition, some payors require an evaluation by a medical geneticist, a genetic counselor or both before any genetic testing can be covered.

Below is a summary of the most commonly ordered tests for a child newly diagnosed with a neurodevelopmental disorder, along with the Current Procedural Terminology (CPT) code and cost billed to insurance.

Reference:

1. Rodan LH, Stoler J, Chen E, Geleske T; Council on Genetics. Genetic evaluation of the child with intellectual disability or global developmental delay: clinical report. Pediatrics. 2025;156(1):e2025072219. doi:10.1542/peds.2025-072219