Array comparative genomic hybridization in global developmental delay.
OBJECTIVE
Array-based comparative genomic hybridization (array CGH) is an emerging technology that allows for the genome-wide detection of DNA copy number changes (CNC) such as deletions or duplications. In this study, array-based CGH was applied to a consecutive series of children with previously undiagnosed non-syndromal global developmental delay (GDD) to assess potential etiologic yield.


METHODS
The children in this study were drawn from a previously reported consecutive series of children with well-defined GDD. Almost all subjects had undergone prior karyotyping and neuroimaging studies with non-diagnostic results. Array-based CGH was undertaken using the SignatureChip(R) (1887 BACs representing 622 loci) with abnormalities verified by subsequent FISH analysis and testing of parents to distinguish between pathogenic and familial non-pathogenic variants.


RESULTS
On CGH analysis in our study, 6 of 94 children (6.4%) had a causally related pathogenic CNC. Three were sub-telomeric in location. An analysis of a variety of clinical factors revealed that only the presence of minor dysmorphic features (<3) was predictive of etiologic yield on CGH analysis (4/26 vs. 2/68, P = 0.05). Severity of delay was not found to be predictive.


CONCLUSIONS
In children with non-syndromal GDD, array-based CGH has an etiologic yield of 6.4%. This suggests that this emerging technology may be of diagnostic value when applied subsequent to detailed history, physical examination, and targeted laboratory testing. Array CGH may merit consideration as a first-tier test in the context of a child with unexplained GDD.
Shevell
M I
MI
Department of Pediatrics, McGill University, Montreal, Quebec, Canada. michael.shevell@muhc.mcgill.ca
Bejjani
B A
BA
Srour
M
M
Rorem
E A
EA
Hall
N
N
Shaffer
L G
LG
D002675:Child, Preschool; D002869:Chromosome Aberrations; D002658:Developmental Disabilities / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D005192:Family Health; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization / Q000379:methods*; D010290:Parents; D010641:Phenotype