The advantages and disadvantages of chromosomal microarrays are highlighted in a recent article and a related editorial (NEJM 2012; 367: 2175-84, 2249-51).

Chromosomal microarrays can detect almost all of the chromosomal imbalances detected with conventional cytogenetic analysis.  They are recommended as a first-tier test for postnatal developmental delays, autism spectrum, or with multiple congenital anomalies.  Clinically significant findings occur in 15% of those with normal conventional karyotypes.

Specific advantages of microarrays:

• Higher resolution
• Faster turnaround due to automation
• Does not require dividing cells (useful in fetal death)
• Eliminates need to culture amniocytes or chorionic villi

Major downside:

• In a few percent, may detect copy-number variant of uncertain clinical significance
• Increased cost

The referenced study compared chromosomal microarray to karyotyping and enrolled 4406 women at 29 centers who were undergoing prenatal diagnosis.  Indications for screening included advanced maternal age (47%), abnormal result on Down’s syndrome screening (19%), structural abnormalities on ultrasonography (25%), and other indications (9%) (some had multiple indications).

The microarrays were of two varieties.  The first microarray (71% of cases) consisted of a fourplex array with each array consisting of 44,000 oligonucleotide probes.  The second platform (29% of cases) contained 1.8 million  oligonucleotide probes.

Key Findings:

• Microarray identified all of the abnormalities on conventional karyotyping except for balanced translocations (no loss of genetic material).
• There were 94 of 3822 fetal samples with copy-number variants of uncertain clinical significance (see blog reference below).  Subsequently, 30 of these were classified as pathogenic and 8 as benign.
• In samples with normal karyotypes, microarray identified clinically relevant findings in 6% of those with a structural abnormality and 1.7% of those with advanced maternal age or positive Down’s syndrome screening.

The implications of this study and related studies are that microarray has a role in prenatal evaluation of structural abnormalities.  Ultimately, whole-exome sequencing will likely supersede microarray analysis and further the conundrum of interpreting abnormalities of uncertain clinical significance.

Related blog entry:

• “It is never boring to be a physician” | gutsandgrowth