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Guidance from the American Academy of Pediatrics covers multiple genetic testing approaches to diagnosing developmental delay and intellectual disability.

A clinical report issued by the American Academy of Pediatrics and published online in Pediatrics offers guidance for the pediatrician regarding the genetic evaluation of developmental delay/intellectual disability.

“Genetic neurodevelopmental disorders are common in the pediatric population, and establishing a specific diagnosis early provides multiple benefits including prognostication, surveillance for disorder-related complications, accurate recurrence risk, and specific management,” the study team wrote.

Lance Rodan, MD, and colleagues explained that genetic causes can be broadly defined as the following:

• chromosomal
• monogenic
• imprinting defects
• oligo/polygenic

The researchers further noted that genetic testing should be selected by phenotype when possible. If medical history, family history, clinical examination, and corollary testing do not lead to a suspected diagnosis, an agnostic or “hypothesis-free” approach is proposed. This approach considers diagnostic yield, test cost and complexity, and potential impact of the results.

Tiered Approach to Genetic Testing

A tiered agnostic approach is proposed based on diagnostic yield and practical considerations:

Tier 1: genome or exome sequencing and chromosome microarray;

Tier 2: Fragile X testing and metabolic testing for inborn errors of metabolism;

Tier 3: testing aimed at identifying genetic etiologies that may have been missed in the first two tiers, including consideration of an imprinting disorder, trinucleotide disorders, mitochondrial DNA testing, karyotype evaluation for balanced chromosome rearrangements, and broad screening for intragenic deletions/duplications that may have been missed.

The Role of Pediatricians & Other Considerations

“Genetic neurodevelopmental disorders are common in the pediatric population, and it is vital for the general pediatrician to have an approach for their initial evaluation,” Dr. Rodan and colleagues wrote. “Establishing a genetic diagnosis early provides multiple benefits.”

Further, they noted that, when possible, genetic testing should be chosen based on phenotype, “but in many cases, an agnostic approach may be utilized.”

The AAP has issued recommendations for this agnostic approach, Dr. Rodan and colleagues noted, based on diagnostic yield and also on practical considerations including test complexity and impact on management.

“These recommendations for initial testing do not preclude further evaluation by relevant subspecialists as necessary, including neurologists, developmental pediatricians, and clinical geneticists,” the researchers wrote.