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This sounds like a pretty straight forward question that should have a simple single sentence definition. This is the term we so often use when speaking about the chromosome 18 conditions, but it is not really the correct term to use.
Historically, from back when chromosome abnormalities were first discovered to twenty-five years ago, a chromosome abnormality was diagnosed using a light microscope. Even the best microscopic chromosome evaluation (called a karyotype) could only detect a missing piece or a duplicated piece of chromosome if it included at least 5,000,000 base pairs (units) of DNA. Although chromosome 18 has the fewest genes per length of any of the human chromosomes, five million base pairs of DNA could still include from 3 to 23 genes. A deletion or duplication smaller than five million base pairs would not have been detected, meaning that many chromosome abnormalities were missed. People were told their chromosomes were normal when they we not because the test was not high enough resolution to detect it. But that was the most advanced technology of the time. If a chromosome deletion or duplication was large enough to be identified using this methodology, then it most assuredly had a negative health effect.
Today the testing is done as a DNA test. The difference is like comparing the detail you can learn from a single page map of the United States to Google Maps. With DNA testing, we no longer miss those smaller chromosome abnormalities. You would think this is wonderful and clarifying news and that all the small chromosome abnormalities previously missed are identified. But miraculous advances are not without their surprises and complications. The DNA testing technology now exists to detect even a single base pair deletion or duplication. What was learned from that analysis is that each of us has, on average, fifty deletions or duplications that are 50 base pairs of DNA or larger. The smaller ones are more frequent than the larger ones. The deletions or duplications that are larger than 100,000 base pairs are less common, with each of us on average having only 10 of these. Most of these differences in the number of copies of a section of DNA are likely between genes and therefore inconsequential - these are referred to as copy number variations (CNVs). However, the size of the DNA change is not the determining factor when it comes to potential negative health implications because there are some genes for which a deletion or duplication of even 1 base pair of DNA is sufficient to cause health issues. The TCF4 gene on chromosome 18 is such a gene. But most of the time, when a chromosome deletion or duplication is identified using this methodology, it has no negative health effect.
The microscopic testing that identified chromosome abnormalities missed many consequential small deletions and duplications, and the DNA testing that identified CNVs included many that are inconsequential. This is why most DNA level tests are not the highest possible resolution and are designed to identify only gene-sized deletions or duplications of several thousand base pairs of DNA. However, the size alone of the deletion or duplication is not the key determinant as to whether it has negative health consequences; what matters is the content of that deletion or duplication and if the genes included have functions that are sensitive to the gene copy number. There are numerous databases that are collecting this information, in addition to our own, which focused exclusively on the effects of gene copy number variation for the genes on chromosome 18.
Neither of the terms discussed so far, “chromosome abnormality” or “CNV,” capture what we mean when we are talking about the type of condition our members care about. The term that includes all three classes: 1) the classic chromosome abnormalities, plus 2) large copy number changes too small to be detected microscopically, plus 3) just those CNVs that impact health, is “Genomic Disorders.” Although this is a newer term and not yet in common usage, the collection of conditions it describes are not rare even though the individual conditions within the collective are rare. In fact, there are over one million Americans with intellectual disabilities due to a genomic disorder. Plus, there are likely an unknown number who have later onset conditions due to a genomic disorder. The impact that these types of genomic changes have on adult health are just now beginning to be appreciated.
Getting the term Genomic Disorder to be at the tip of your tongue instead of the term “chromosome abnormality” is a challenge, but if we begin to use it then slowly it will come into common usage and people will begin to understand the implications. I need to practice my opening line when someone asks me what chromosome 18 is - I need to be ready to say that the chromosome 18 conditions are Genomic Disorders in the same class of conditions as Down Syndrome. Hopefully that will anchor the term and the chromosome 18 conditions to something familiar to the recipient.
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