What's in a Name?

Families often ask us - what is the “official name” for dup15q syndrome? After all, other syndromes have official sounding names. Mutations in the MECP2 gene lead to Rett syndrome. Individuals with trisomy 21 have Down syndrome. Deletions of the critical stretch of genes located on chromosome 15q11.2-13.1 results in either Angelman syndrome or Prader-Willi syndrome (depending on the chromosome’s parent of origin). But too many copies of genes from the same region results in - what exactly?

Over the years there have been many different names. Families receiving a diagnosis for their child 20 years ago may have been told that their child had "partial trisomy 15", "satellite marker chromosome 15", "duplicated material from chromosome 15", "inverted duplication of chromosome 15", or interstitial duplication of chromosome 15". Even considering that chromosome 15q duplications come in many shapes and sizes - isodicentric duplications [idic(15)] or interstitial duplications [int dup(15)], with various copy numbers and areas of duplication - many of these names are just different ways of describing the same thing. And as one might expect, this proliferation of names has long been a source of confusion.

We’ve been consulting with our Professional Advisory Board for a sensible naming convention. What they proposed is “chromosome 15q11.2-13.1 duplication syndrome”, or “dup15q syndrome” for short.

Why did they pick such a coordinate-heavy name? In part it was a desire to clearly describe the regions of 15q whose duplication will result in comparable clinical issues - a difficult task since the various types of chromosome 15q duplications play out clinically in slightly different ways, and even within the same class of duplication the clinical outcomes can vary quite widely from individual to individual. So in defining which of these duplications to include in the syndrome, one has to decide where to draw the line - lumping together the classes of duplications that produce sufficiently clinically similar outcomes and splitting out those that do not. The view of our professional advisors was that the cytogenetic coordinates “15q11.2-13.1” define the common denominator - that stretch of genes, which is also known as the Prader-Willi/Angelman critical region - whose duplications, either isodicentric or interstitial, are thought to disrupt normal development in related ways and produce recognizably similar clinical effects.

The short-form name is of course far easier to articulate, albeit at the cost of being less descriptive. But besides brevity the main virtue of “dup15q syndrome” is that it is already a part of existing usage. Increasingly researchers and clinicians, writing in grant applications or research papers, or speaking at professional conferences, use the collective term “dup15q syndrome” to encompass the various types of duplications of genes in this region. Such name recognition in the research community is an extremely valuable thing from the perspective of families.

But if the syndrome - in both name and meaning - includes only those “core” 15q duplications spanning the PWS/AS critical region (15q11.2-13.1), what should we call the 15q duplications that lie outside of that region? Individuals with these duplications generally experience distinctly different clinical characteristics compared to the core 15q duplications. Whatever the clinical outcome, it is in many cases uncertain whether the 15q duplications in question are even the cause. After all, there are many people with those duplications who report no clinical problems of any sort. That’s why the recommendation of our Professional Advisory Board was to describe these duplications simply as just that - duplications. So, for example, for the microduplications near coordinates 15q11.2 or 15q13.3, just over the edge of the PWS/AS critical region we would write “15q11.2 duplication” and “15q13.3 duplication” (or “dup15q11.2” and “dup15q13.3”, for short).

Some parents have asked, why not name dup15q syndrome after one or several of the medical researchers who first identified and characterized the syndrome, as with Rett or Angelman syndromes? We did float this idea, but our Professional Advisory Board - which itself is comprised of many of those (such as Brenda Finucane, Carolyn Schanen, Edwin Cook, and Agatino Battaglia) who would rightly be considered dup15q pioneers - was of the view that naming syndromes after people is generally a bad habit, and particularly inappropriate in the case of dup15q syndrome. Such names do little to convey the nature of the syndrome in question, and the hoped-for mnemonic benefits are often fairly minimal, so descriptive names adopted according to standard naming conventions are increasingly preferred by medical professionals.