Evidence Report: Genetic and metabolic testing on children with global developmental delay [RETIRED]

Abstract

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. AAN= : American Academy of Neurology; BAC= : bacterial artificial chromosome; CDG= : congenital disorders of glycosylation; DQ= : developmental quotient; DXL= : definite X-linkage; GDD= : global developmental delay; ID= : intellectual disability; IEM= : inborn errors of metabolism; PXL= : possible X-linkage; UXL= : unknown X-linkage; XLID= : X-linked intellectual disability