The Karyotype: Are Chromosome Studies Necessary Anymore?

Bruce Buehler, MD, Pediatrics, General, 12:22PM Feb 16, 2011

For the past 30 years, prometaphase, microscopic studies of the chromosomes from each cell has been the genetic test for individuals with delays, multiple anomalies, or supected syndromes. This began with Down syndrome (trisomy 21) and Turner Syndrome (X0) karyotypes. Microarray (comparative genomic hybridization, or CGH) can identify thousands of genes unidentifiable by microscopic study of a chromosome. It can be done on a small blood sample in a short period of time. Working at the gene level improves diagnostic efficiency and identifies very small deletions or duplications not seen on a karyotype.

For the past 5 years, karyotype and microarray were ordered together for genetic studies. Yet microarray technology has rapidly evolved to looking at small changes within a gene, leading to sophisticated genetic disease identification, while karyotypes remain unchanged.

With the emergence of microarray technology, what is the role of a standard chromosome study as a first step in the diagnosis of multiple congenital anomalies or developmental delays? The American College of Medical Genetics recently published a statement that microarray studies are the genetic study of choice in unknown syndromes and developmental delays.* This is partly in response to the insurance companies that have been unwilling to pay for microarray, claiming it is experimental. It is now clear that microarray is a reliable genetic diagnostic test with greater potential than a karyotype.

A karyotype may remain useful for translocations and well known chromosome abnormalities like Down syndrome, Trisomy 13, or Trisomy 18, but even that will soon be replaced by the next generation of microarray technology.

For the clinician, it is best for your patient to order microarray as your first broad genetic test. Karyotype should be reserved for family studies and a few known large chromosome syndromes. The payors will be less willing to pay for both microarray and karyotype, so microarray is the most efficient test. This is a major shift for clinicians, but it is only one of the changes in laboratory testing emerging from new technology.

*The American College of Medical Genetics guideline was published in Genetics in Medicine in November 2010 and is available at http://www.acmg.net/StaticContent/PPG/Array_based_technology_and_recommendations_for.13.pdf.

regards, taniafdi ^_^