The Frontal Cortex

Williams Syndrome

David Dobbs has a wonderful article in the most recent Times Magazine on Williams syndrome, a development disorder that results in a bizarre mixture of cognitive strengths and deficits:

Williams syndrome rises from a genetic accident during meiosis, when DNA’s double helix is divided into two separate strands, each strand then becoming the genetic material in egg or sperm. Normally the two strands part cleanly, like a zipper’s two halves. But in Williams, about 25 teeth in one of the zippers — 25 genes out of 30,000 in egg or sperm — are torn loose during this parting. When that strand joins another from the other parent to eventually form an embryo, the segment of the DNA missing those 25 genes can’t do its work.

The resulting cognitive deficits lie mainly in the realm of abstract thought. Many with Williams have so vague a concept of space, for instance, that even as adults they will fail at six-piece jigsaw puzzles, easily get lost, draw like a preschooler and struggle to replicate a simple T or X shape built with a half-dozen building blocks. Few can balance a checkbook. These deficits generally erase about 35 points from whatever I.Q. the person would have inherited without the deletion. Since the average I.Q. is 100, this leaves most people with Williams with I.Q.’s in the 60s. Though some can hold simple jobs, they require assistance managing their lives.

The low I.Q., however, ignores two traits that define Williams more distinctly than do its deficits: an exuberant gregariousness and near-normal language skills. Williams people talk a lot, and they talk with pretty much anyone. They appear to truly lack social fear. Indeed, functional brain scans have shown that the brain’s main fear processor, the amygdala, which in most of us shows heightened activity when we see angry or worried faces, shows no reaction when a person with Williams views such faces. It’s as if they see all faces as friendly.

People with Williams tend to lack not just social fear but also social savvy. Lost on them are many meanings, machinations, ideas and intentions that most of us infer from facial expression, body language, context and stock phrasings. If you’re talking with someone with Williams syndrome and look at your watch and say: “Oh, my, look at the time! Well it’s been awfully nice talking with you . . . ,” your conversational partner may well smile brightly, agree that “this is nice” and ask if you’ve ever gone to Disney World. Because of this — and because many of us feel uneasy with people with cognitive disorders, or for that matter with anyone profoundly unlike us — people with Williams can have trouble deepening relationships. This saddens and frustrates them. They know no strangers but can claim few friends.

Dobbs interviews some neuroscientists who are attempting to use Williams syndrome as a window into human sociality:

Julie R. Korenberg, a neurogeneticist at Cedars-Sinai Medical Center and at the University of California, Los Angeles, who has helped define the Williams deletion and explore its effects, believes the value of Williams syndrome in examining such questions is almost impossible to overstate. “We’ve long figured that major behavioral traits rose in indirect fashion from a wide array of genes,” Korenberg says. “But here we have this really tiny genetic deletion — of the 20-some-odd genes missing, probably just 3 to 6 create the cognitive and social effects — that reliably creates a distinctive behavioral profile. Williams isn’t just a fascinating mix of traits. It is the most compelling model available for studying the genetic bases of human behavior.”

I agree, of course, that Williams syndrome is a promising paradigm with which to study the underlying genetics and architecture of the social mind. But it’s also easy to overinterpret the genetic specificity of the disorder. I used to work with a scientist who spent his days creating knockout mice. Needless to say, he was a skeptical man, and liked to poke holes in research that tried to draw lofty conclusions from small genetic deletions. He often compared the brain to a car engine. Disconnect the battery cable and the engine won’t work. Thus, a scientist might conclude that the key part of the engine is the battery cable since its loss equals a loss of function. Obviously, such a conclusion is a silly oversimplification. A car engine, like a brain, is a complicated machine. It requires an endless number of interlocking parts in order to work. Many of our genes (especially our brain genes) code for multiple proteins, or express proteins that have a variety of purposes, and mutating even a small snippet of DNA can cause a mess of inexplicable proportion. This doesn’t mean that the erased gene was particularly important. It simply means that the living thing was designed as an inviolable whole. To think otherwise is to risk falling for the “inductive fallacy” of knockout experiments, or what Henri Bergson called “the illusion of retrospective determinism.”

I’m also a wee bit skeptical of the preliminary anatomical findings of Williams researchers, which is that there’s a “dead connection” between the orbitofrontal cortex and the amygdala. Considering that the exact same anatomical mechanism has been proposed for the psychopathic brain, it’s hard to argue that this is the defining neural correlate of Williams syndrome.

But give the whole article a read. It’s fascinating. For a rather different take on Williams syndrome, be sure to check out Oliver Sacks forthcoming book, which includes a chapter on the hypermusicality of people with Williams syndrome.

Comments

  1. #1 tekel
    July 16, 2007

    But in Williams, about 25 teeth in one of the zippers — 25 genes out of 30,000 in egg or sperm — are torn loose during this parting.

    Maybe I’m nitpicking, but this seems like a grossly oversimplified description of a chromosomal nondisjunction event. I realize the article is in in Times Magazine and not in Nature, but Times does a disservice to their readers by dumbing down the basic science. A “gene” is not the same thing as a DNA nucleotide, and the zipper analogy works much better for the latter than it does for the former.

    This description fails for both those who are scientifically literate and those who are totally ignorant of cellular reproduction and genetics. Anyone who has had a high school biology class in the last 15 years will read that and recognize that it’s not quite right; anyone who has never had a cell class won’t understand any more than they did before.

  2. #2 blaine
    July 17, 2007

    Interesting … using the zipper analogy, would it be a better to say that the deletion was the “chipping off” of some of the coating on the teeth of the zipper as it was pulled apart?

  3. #3 Phil
    February 9, 2008

    Hello there. I recently started seeing a girl who has williams. I knew nothing about it nor did I suspect anything was wrong with her until she told me she had williams. I did some reading about it and although she does have some trouble with things like computers, she seems fairly righton. I think shes perfect but thats not what im hear for. We as people have been conditioned to think differently of those with mental disabilities and I was wondering if im evil because I really like this girl and I want to pursue a relationship with her. Im telling you, her personality is like a vaccum and it just sucked me right in. She sweet, cute, fun, and everything ive been looking for. Ive never dated anyone with mental disabilities and I didnt know I was until she told me lol. I dont see her as a person with mental disabilities. I dont see her like that at all. Im just wondering if I can treat this like a normal relationship as thats how it feels to me. Thank you for your time.

  4. #4 lindsay
    November 13, 2011

    i know what its like to have willAMSSYNDROME BECUSE I HAVE IT AND ITS NOT EAS FOR ME TO HAVE A DISSABILTY BUT I LOVE PEOLE AND YES I FEAR EXCPTANCE AND I DONT HAVE ALOT OF FRIENDS