Genetic Evaluation of the Child With Intellectual Disability or Global Developmental Delay: Clinical Report

Area of Science:

• Pediatric Genetics
• Neurodevelopmental Disorders
• Clinical Diagnostics

Background:

• Genetic neurodevelopmental disorders are prevalent in children, necessitating early diagnosis for improved outcomes.
• Timely diagnosis facilitates prognostication, complication surveillance, recurrence risk assessment, and targeted management strategies.

Purpose of the Study:

• To provide a practical approach for the genetic evaluation of developmental delay/intellectual disability for general pediatricians.
• To guide the selection of genetic testing, prioritizing phenotype-guided strategies when possible.

Main Methods:

• Review of clinical features to guide phenotype-directed genetic testing.
• Recommendations for an agnostic (hypothesis-free) genetic testing approach when phenotype is unclear.
• Consideration of diagnostic yield, test complexity, and management impact for agnostic testing.

Main Results:

• Phenotype-guided genetic testing is preferred when distinguishing clinical features are present.
• An agnostic approach is recommended when a specific diagnosis cannot be determined by phenotype.
• Guidance considers practical factors for agnostic genetic testing strategies.

Conclusions:

• A systematic approach to genetic evaluation is crucial for pediatric developmental delay/intellectual disability.
• Phenotype-guided and agnostic testing strategies offer valuable diagnostic pathways.
• This guidance complements, but does not replace, subspecialist evaluations.