Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

Neurology. 2011 Oct 25;77(17):1629-35. doi: 10.1212/WNL.0b013e3182345896. Epub 2011 Sep 28.


Objective: To systematically review the evidence concerning the diagnostic yield of genetic and metabolic evaluation of children with global developmental delay or intellectual disability (GDD/ID).

Methods: Relevant literature was reviewed, abstracted, and classified according to the 4-tiered American Academy of Neurology classification of evidence scheme.

Results and conclusions: In patients with GDD/ID, microarray testing is diagnostic on average in 7.8% (Class III), G-banded karyotyping is abnormal in at least 4% (Class II and III), and subtelomeric fluorescence in situ hybridization is positive in 3.5% (Class I, II, and III). Testing for X-linked ID genes has a yield of up to 42% in males with an appropriate family history (Class III). FMR1 testing shows full expansion in at least 2% of patients with mild to moderate GDD/ID (Class II and III), and MeCP2 testing is diagnostic in 1.5% of females with moderate to severe GDD/ID (Class III). Tests for metabolic disorders have a yield of up to 5%, and tests for congenital disorders of glycosylation and cerebral creatine disorders have yields of up to 2.8% (Class III). Several genetic and metabolic screening tests have been shown to have a better than 1% diagnostic yield in selected populations of children with GDD/ID. These values should be among the many factors considered in planning the laboratory evaluation of such children.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Advisory Committees / standards*
  • Developmental Disabilities* / diagnosis
  • Developmental Disabilities* / genetics
  • Developmental Disabilities* / metabolism
  • Evidence-Based Medicine
  • Family Health
  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Genetic Testing / methods*
  • Genetic Testing / standards
  • Histone Demethylases
  • Homeodomain Proteins / genetics
  • Humans
  • Male
  • Metabolism, Inborn Errors / complications
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism
  • Methyl-CpG-Binding Protein 2 / genetics
  • Microarray Analysis / methods
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Neurology / standards*
  • Oxidoreductases, N-Demethylating / genetics
  • Plasma Membrane Neurotransmitter Transport Proteins / genetics
  • Transcription Factors / genetics


  • ARX protein, human
  • FMR1 protein, human
  • Homeodomain Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Nerve Tissue Proteins
  • Plasma Membrane Neurotransmitter Transport Proteins
  • SLC6A8 protein, human
  • Transcription Factors
  • Fragile X Mental Retardation Protein
  • Histone Demethylases
  • KDM5C protein, human
  • Oxidoreductases, N-Demethylating