What's in a Name?

Today's post is the first in a two-part series about the importance of the terms we use. It was written by Dr. Jannine Cody, president of the Registry and director of the Chromosome 18 Clinical Research Center!

I once read an article in a medical journal in which the author made the comment that Trisomy 21 was the leading cause of Down syndrome. My first thought was, “Well, duh!” I wondered what else he thought could cause Down syndrome...Maybe bad karma? But I have come to appreciate that there are fundamentally different approaches to describing a condition. In the case of Down syndrome and trisomy 21, the two terms seem synonymous and are often used interchangeably. But, in our world, where each individual has a slightly different chromosome change, the terms “trisomy 21” and “Down syndrome” are significantly different. The term “trisomy 21” describes a genetic change, namely, an extra copy of chromosome 21. The term “Down syndrome” describes the collection of medical and developmental issues that are caused by the extra chromosome. We need to understand the difference and be sure we use the correct terms. If we don’t, then we inadvertently send the wrong message to the medical community.

A syndrome is a group of characteristics that often occur together and therefore are presumed to have the same underlying cause. So, syndromes are defined by the physical characteristics or medical findings (what I usually call the “phenotype”). In many cases, the cause is unknown – or, at least, the cause was unknown at the time that someone recognizes and names a group of characteristics that co-occur in more than one person. An example is Pitt Hopkins syndrome. This is a group of characteristics that includes a broad mouth with full lips, breathing abnormalities, and severe intellectual disability. People who fit this clinical description were said to have Pitt Hopkins syndrome. Now we know that the syndrome has 3 possible causes. In other words, abnormalities in one of three different genes can cause Pitt Hopkins syndrome. So now they are renamed Pitt Hopkins-like I, Pitt Hopkins-like II etc. This renaming aligns the genetic cause (genotype) with the clinical presentation (phenotype).

However, many chromosome abnormalities, like 18p-, 18q-, Ring 18, Tetrasomy 18p and Trisomy 18 are defined by the genetic abnormality rather than the physical characteristics. In the 1960s, chromosome analysis was just starting to be performed on babies with severe developmental problems and multiple malformations in the hopes that it would provide answers about the cause of their problems. Indeed, these and other chromosome abnormalities were found in some of these children. The next step was to define the characteristics of people with each of these “syndromes.”

Hopefully, you have noticed the inconsistency here. The term syndrome should not have been applied here. These conditions were not defined by their physical characteristics but by their underlying genetic change. However, some reverse thinking was applied. Researchers looked for a consistent set of features that would co-occur with each chromosome abnormality. Rather than starting from the physical characteristics (or syndrome) and looking for the genetic change, they started from the genetic change and looked for the physical characteristics. As if each chromosome abnormality was a single entity.

There is another reason that the word “syndrome” is not appropriate to use for chromosome abnormalities. On the molecular level, chromosome abnormalities are very different.

18q- is an excellent illustration of this point. First, we must ask the question, “What is 18q-?” The answer might seem straightforward at first…It is a deletion of a part of chromosome 18q. But what part? You will notice that there is no medical problem, no phenotype associated with this definition. 18q- (and the other chromosome 18 abnormalities) are defined by the genotype. But which genotype? I could easily find 5 people, all with 18q-, with deletions do not overlap with each other. So, at the molecular level they all have unique causes for their condition, but yet they all have 18q-. At some level, people who do not really want to think about it too hard will want to lump them all together for simplicity sake. But for parents who are trying to find other families with children like theirs, who are trying to learn about specific prognoses and treatments, the finer we can define the condition the better. So we better stop using the word syndrome because it implies things to the medical community that are not accurate about our conditions.

So, this leads to our next question...What term should we use instead of the word "syndrome"? That will be the topic of our next post!