Chromosomal Microarray Analysis for Intellectual Disabilities
What is the need to strive for a genetic diagnosis?
A diagnostic chromosomal microarray will provide the medical care team, family, and patient with a firm diagnosis.
- In several instances, ineffective or contraindicated therapies need not be initiated or stopped if they are already underway. The focus could then shift to appropriate medical care.
- In some children educational planning may be changed based on the test results.
- Some families might choose to limit medical care to palliative measures based on a diagnosis associated with a poor prognosis.
- The results of family testing to determine risk for future children can strongly influence reproductive choices, both positively when the risk appears low and negatively when the risk appears high.
- Establishing a specific genetic diagnosis by microarray can render moot extensive testing that most patients otherwise undergo for the diagnostic evaluation of ID: blood and urine tests for metabolic disorders, multiple brain MRIs requiring sedation, electroencephalograms, lumbar punctures for metabolic tests of spinal fluid, and skin and muscle biopsies.
- A positive microarray, especially when obtained early in the workup of a patient, could reduce both individual and societal costs associated with testing and medical care. (Michelson 2011; Tirosh & Jaffe 2011; Van Karnebeek & Stockler 2012)
Microarray testing is widely available and its cost has been steadily declining. It is foreseeable that, as the cost of full exome sequencing comes down, whole exome testing may be the best way to perform the primary sequencing of the chromosomes, with the microarray remaining the best way to detect CNVs. The full interpretation of genomic testing would consist of an abnormal microarray, or a normal microarray in conjunction with whole exome sequencing. As technology moves forward, this prediction will require refinement.
Neurologists and geneticists tend to order CMA testing more frequently than other specialists. (Coulter et al. 2011) Of 49 respondents to a 2012 questionnaire-based survey sent to members of the AAN Child Neurology Section, all but one ordered microarray testing on a routine basis. 4 commented that they would refer the patient to colleagues in genetic medicine also to decide if the test should be ordered. Their reasons for referral were that either the approval process was easier for the medical geneticist or that their institution required a geneticist’s prior approval. Clinical utility, comfort with ordering and interpreting the test and ease of obtaining insurance coverage were the detriments for ordering the test. Unfamiliarity with the test, its interpretation, and difficulty of obtaining insurance coverage in some regions were the reasons for not ordering the tests. In one medical center, where more than a dozen health care providers evaluated patients with ID and dysmorphism, uninfluenced by insurance coverage, microarray ordering and testing frequencies varied from “almost always” to “never.” (Unpublished AAN survey 2012) This survey result, although limited by a 15% response rate, accords with the general experience indicating that the application of this technology still varies much. Large longitudinal studies of test ordering practices have not yet been done. This is one reason for the unavailability of data associated with utilization, costs and benefits. However, small sample studies have shown that positive test findings result in significant changes in medical care. (Coulter et al. 2011; Saam et al. 2008)
Received 13 July 2005 | Accepted 9 January 2006
Technology Insight: querying the genome with microarrays—progress and hope for neurological disease