title: Evidence report: Genetic and metabolic testing on children with global developmental delay [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
abstract: 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).
  
  
  
  Relevant literature was reviewed, abstracted, and classified according to the 4-tiered American Academy of Neurology classification of evidence scheme.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Michelson
authors.forename: M I
authors.initials: MI
authors.lastname: Shevell
authors.forename: E H
authors.initials: EH
authors.lastname: Sherr
authors.forename: J B
authors.initials: JB
authors.lastname: Moeschler
authors.forename: A L
authors.initials: AL
authors.lastname: Gropman
authors.forename: S
authors.initials: S
authors.lastname: Ashwal
mesh_terms: D026683:Advisory Committees / Q000592:standards*; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D019317:Evidence-Based Medicine; D005192:Family Health; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005820:Genetic Testing / Q000379:methods* / Q000592:standards; D056466:Histone Demethylases; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D046228:Microarray Analysis / Q000379:methods; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009462:Neurology / Q000592:standards*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D056466:Histone Demethylases; D018398:Homeodomain Proteins; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D010089:Oxidoreductases, N-Demethylating; D050480:Plasma Membrane Neurotransmitter Transport Proteins; D014157:Transcription Factors; C469264:ARX protein, human; C497683:FMR1 protein, human; C497392:MECP2 protein, human; C094770:SLC6A8 protein, human; C086877:KDM5C protein, human