For decades, the karyotype was the standard first test for children with developmental delay, intellectual disability or birth defects. Chromosomal microarray has now replaced it as the recommended first-tier test for these conditions.
Resolution
A standard G-banded karyotype detects changes of approximately 5 to 10 million base pairs or larger. Chromosomal microarray detects deletions and duplications more than a hundred times smaller across the entire genome, including the microdeletion syndromes that are a common cause of developmental disorders.
Diagnostic Yield
In children with developmental delay, intellectual disability, autism spectrum disorder or multiple congenital anomalies, chromosomal microarray identifies a causative change in about 15 to 20% of cases, compared with about 3% for karyotyping. In pregnancies with fetal structural anomalies and a normal karyotype, microarray identifies a clinically significant change in about 6% of cases.
Additional Information from SNP Arrays
SNP-based microarrays also detect regions of absence of heterozygosity. These can indicate uniparental disomy, which causes imprinting disorders such as Prader-Willi syndrome, or shared ancestry between parents, which increases the chance of autosomal recessive conditions. SNP arrays can also detect triploidy.
Where Karyotyping Still Matters
Microarray does not detect balanced rearrangements, because no genetic material is gained or lost. Karyotyping remains essential when a balanced translocation is suspected, for couples with recurrent pregnancy loss, and to determine the mechanism behind an unbalanced change found by microarray.
Uncertain Results
Because microarray examines the whole genome, it sometimes identifies copy number variants of uncertain significance. Testing the parents, reviewing population databases and following updated evidence help clarify these findings. Pre-test counselling prepares families for this possibility.