Williams Syndrome – What Do These Genes Do?

When you know someone who has, or might have Williams Syndrome, often your first reaction is to begin to search for information on the internet.

If you’ve done this, you’ll no doubt have read that there are many possible symptoms. As a parent you’re often aware of the slow development of your child. You often see they have an elfin face, their teeth may be small and gappy, they are often smaller than any brothers or sisters.

Physically they may be diagnosed with narrowing of the arteries, or a heart murmur, they may have problems with constipation or with hernias.

Williams Syndrome symptoms also include many effects on the intellectual aspects of the person affected. They often show learning disability, poor physical coordination, very poor numeric skills, surprisingly well developed verbal and musical skills…

When you’re searching for reasons you’ll probably read that Williams Syndrome is caused by a microdeletion of DNA from chromosome 7.

It’s only natural you will ask – what does all this mean?

Often we begin with two questions:
1) Is it my fault? Just how or why does the deletion occur?
2) How can deleting, losing, just a few genes cause all the symptoms of Williams Syndrome?

At a basic level, the first question is easier to understand and is explained in a related article on this site “Williams Syndrome Deletion – Why?” and on a more detailed video. The technical stuff about why and how a deletion occurs is explained there in really easy ideas and language.

So now we’re left wondering, what do these genes do? How can deleting or losing just a few genes cause all the symptoms of Williams Syndrome?

Again we’ll start with the easy bit.

The gene that lies at the center of the Williams Syndrome deletion contains the code for a protein called elastin. Elastin is an important protein in forming a specific type of smooth muscle, making that muscle more elastic. This type of smooth muscle has many functions in our bodies but one important role is it forms a layer inside all our arteries. When one copy of the elastin is missing or damaged, people often get narrowing of the arteries as they don’t stretch as much as they should. The most common diagnosis here is aortic stenosis which is pretty characteristic of Williams Syndrome. Other effects might include more frequent incidence of hernias or diverticulitis.

But more than 20 other genes are also affected and their complex story is still being unravelled. The overall picture is still very patchy. Sometimes it might be possible to associate the absence of a certain gene with a specific defect while the deletion of other genes has more subtle or widespread effects.

There is some evidence that a gene called GTF2IRD1 (this technical name is important to the medical geneticists that have identified the gene) is important for proper physical development of head and face.

Other genes have a greater influence on the way we develop, understand and use language. We are familiar with the idea that one characteristic of Williams people who have this deletion is that they are over-friendly and chatty. They have surprisingly good verbal skills considering some of their other disabilities. We don’t yet know which genes are specifically involved but we do know that in some people, there is the opposite condition. They have a duplication rather than a deletion of the Williams Syndrome region and have very poor language skills so researchers are working to narrow down the genes responsible.

Other genes such as GTF2I (encoding general transcription factor II, I)  might  be affecting the general learning disability and possibly together with LIMK1 (which encodes the LIM domain kinase 1) is probably involved in the visuospatial construction difficulties.

More specifically, having only one copy of the CLIP2 gene (encoding CAP-GLY domain containing linker protein 2) may contribute to problems with motor coordination.

The absence of the gene for Williams Syndrome Transcription Factor (WSTF), may have much more widespread effects on diverse WS disorders as this interacts with several other gene regulatory systems.

I hope to fill-in some of these information gaps as I read and understand the research papers emerging on the subject.

The hope is that, with better understanding of WIlliams Syndrome, one day will come the potential for more effective treatment. In the present, these insights into the way the brain works, into the ways that we learn and develop skills, at least gives us better insights into how we can teach and support and encourage people affected by Williams to learn and to engage more fully with their world.