Success is very much about seizing opportunities. With all of David’s early issues, we could not address everything at once, but we always looked for opportunities. For example, when he started climbing in the refrigerator we encouraged him (under watchful eyes). See the picture here: Gene deletion versus mutation.
Science is about hard work, but it is also about seizing opportunities. The discovery of penicillin is a classic example. Alexander Fleming made his discovery in a moldy petri dish. The open dish was contaminated by a mold that killed bacteria in the dish. The mold in the dish was accidental, but Fleming’s observation was not. He was a scientist looking for ways to kill bacteria. A few years after the initial discovery, penicillin saved its first life: a child. We need to keep our eyes open for opportunities and we need to make opportunities happen. So how can we do that?
This past week a group of 22q13 deletion syndrome parents took on a challenge. I asked them to identify other children who are most like their own. The goal was to find ways to “cluster” the characteristics of children with 22q13 deletion syndrome, as described in my most recent blog: Splitting, Lumping and Clustering. It was a lot of fun and, just as I suspected, there are groups of kids that are very similar to each other. The information on the Facebook group could be compiled and studied. I would recommend someone do that. The exercise could be expanded. There is a lot to learn. Parents have insights into their children that medical researchers cannot. Categorizing how groups of children are alike and different could speed up research.
This blog is about other, untapped opportunities to look at categories of 22q13 deletion syndrome children. There are special cases we should not overlook.
I hear people say that no two deletions are exactly alike. Not true. There are cases where the deletions are exactly the same. Here is the list: 1) twins (yes, there are twins in our community), 2) unbalanced translocations (my son’s deletion and my niece’s deletion are exactly the same, as are several other children and adults in our extended family), and 3) germ line deletions. I do not know any 22q13 deletion syndrome families with multiple children from germline deletions. I would be interested in hearing of any cases.
I have heard some doctors and scientists say “no two deletions are alike” even though they should know better. We need to exploit these cases to find out what matched deletions have in common and how they differ from each other. Those observations will hint at which aspects are genetic and which are probably not.
There are a lot of 22q13 deletion syndrome children with terminal deletions. There are fewer people with interstitial deletions. What if we take each person with an interstitial deletion and matched them up with someone who’s deletion starts at the same spot on the chromosome? In such a case both people would be missing the same interstitial genes. What can we learn? It is a kind of A minus B experiment. It might tell us a lot about what the genes in common are doing.
Pure SHANK3 deletions
One popular theory about 22q13 deletion syndrome is that SHANK3 mutations act simply by reducing the amount of SHANK3 protein. If a SHANK3 gene is missing altogether, there is no controversy. However, there is an alternative theory that mutations of SHANK3 cause the formation of damaging proteins. The difference is important. In the first case, studying SHANK3 mutations are likely to help anyone with a SHANK3 loss (most people with 22q13 deletion syndrome). In the second case, a cure for SHANK3 mutation is not likely to help most people with 22q13 deletion syndrome. Right now the differences are being studied in mice and rats. As valuable as such research might be, it does not resolve the question in people.
We need a study that specifically compares these two groups, people with SHANK3 mutations and people with complete (or nearly complete) SHANK3 deletions that are small enough to leave other, nearby genes, alone. Once again, we as parents can look at our children, and start listing their characteristics and share the similarities and differences.
I believe parents can be major contributors just by our ability to see similarities and differences in our children. The scientists and clinicians studying our children have all kinds of ideas, but frankly they can use a little guidance. Drug studies are mixing kids with the tiniest mutations and kids with big deletions. Tools to measure vocalizations are being tested on kids that make very few sounds, and their parents already know what those sounds mean and how often their kids make them. We can appreciate that our kids are difficult to understand, but the whole research/investigation process can be improved. The PMSF International Registry has been a big step in the right direction, but listening to the parents explore like-children this week on Facebook, it is clear families are ready to do more.
Splitting, Lumping and Clustering
Defining Phelan McDermid syndrome
Why don’t we have better drugs for 22q13 deletion syndrome?
What do parents want to know?
Is 22q13 deletion syndrome a mitochondrial disorder?
Educating children with 22q13 deletion syndrome
How to fix SHANK3
Have you ever met a child like mine?
How do I know which genes are missing?
How can the same deletion have such different consequences?
22q13 and the hope of precision medicine
22q13 Deletion Syndrome: hypotonia
Understanding gene size
Gene deletions versus mutations: sometimes missing a gene is better.
Is 22q13 deletion syndrome a ciliopathy?
Understanding translocations in 22q13 deletion syndrome: genetics and evolution
Understanding deletion size
Can 22q13 deletion syndrome cause ulcerative colitis?
Can 22q13 deletion syndrome cause cancer?
22q13 deletion syndrome – an introduction