Developmental Delay/Intellectual Disability — Rationale for Testing Children — Clinical Pathway: Primary Care

Developmental Delay/Intellectual Disability Diagnostic Evaluation Clinical Pathway — Primary Care

Rationale for Testing Children with Suspected Developmental Delay/Intellectual Disability (DD/ID)

Recommend comprehensive evaluation for children with DD/ID, including genetic and metabolic testing. American Academy of Pediatrics (AAP) 2014 Guidelines  

If History and Physical Examination Does Not Suggest a Specific Diagnosis

1st Tier Testing
  • Chromosomal microarray and fragile X testing, recommended by:
    • AAP
    • American Academy of Neurology
    • American College of Medical Genetics (ACMG)
  • Reported diagnostic yield ranges from 15 to 20%
2nd and 3rd Tier Testing
  • AAP guidelines also include several metabolic tests early in the evaluation process.
  • Early identification of many inborn errors of metabolism allows timely initiation of specific therapy that halts the progression of the disease and improves outcomes.
  • Reported diagnostic yield of 5%.
  • Therefore, we recommend sending these tests only when specific indications are present in the clinical evaluation.

Additional Diagnostic Testing: Exome and Genome Sequencing

Exome sequencing is recommended as 1st or 2nd tier following microarray if microarray is not diagnostic.

Has a high diagnostic yield of 31%, and up to 53% if DD/ID is associated with other system involvement, dysmorphic features or congenital anomalies.

ACMG Exome and Genome Sequencing for Pediatric Patients with Congenital Anomalies or DD/ID, 2021  

Benefits

Establishing an underlying diagnosis is essential for starting early targeted therapies for treatable disorders.

Clarification of the underlying genetic or metabolic diagnosis allows for improved access to support services, surveillance and prevention of secondary complications, and avoidance of unnecessary testing. It reduces the experience of a diagnostic odyssey, improves our ability to provide family counseling and future planning, and allows for increased access to ongoing and emerging research therapies.