I never know if I should start with disclaimers or end with them. But this time I am starting with one. I am always on the lookout for anything that might be relevant to improving life for people with any of the chromosome 18 conditions. Sometimes I find information that could be directly applicable but mostly I find hints – things to keep an eye on. I recently ran across such a hint that I was pretty excited about even though it is just a hint. However, this hint could be uniquely relevant to helping babies with Trisomy 18 making it worth mentioning. The disclaimer is that this article is about a hint that might just turn out to be relevant, but then maybe not, it is just a hint of hope.
To back up a bit, one of the core questions we need to address is which of the genes on chromosome 18 are responsible for the medical and behavioral consequences of having too many or too few copies of those chromosome 18 genes. One of the ways I work to inform the answer to that question is to daily monitor the new scientific publications concerning each of the 263 genes on chromosome 18. I am trying to determine which are the culprits and which are the bystanders. This information sometimes provides proof and sometimes only hints that a gene may be a consequential culprit or merely a bystander. I keep track of this information on our Gene Dosage Map that can be found on the Chromosome 18 Clinical research Center website (https://wp.uthscsa.edu/chrome-18/). To date, we think that about 90% of the genes are bystanders when it comes to chromosome deletions. For these bystanders, one copy instead of two copies of the gene is quite sufficient for normal functioning. It is less clear how many genes are in each group regarding duplications, but is likely to be similar. We expect to find that there will only be a handful of culprit genes responsible for the characteristics found in people with chromosome 18 duplications (trisomy).
One gene in particular on 18q with some hints that it may be one of the culprits when it is duplicated, as in trisomy 18, is called SMAD2. There are hints (underline and emphasize the word hints) that this gene may play a role in two issues found in some individuals with trisomy 18; Wilms tumor and pulmonary arterial hypertension. A recent publication identified an overactive SMAD2 gene as a cause of arterial pulmonary hypertension. An overactive SMAD2 gene might just be equivalent to having 3 copies of the gene. This publication was authored by a group from a biotech company focused on developing therapies aimed at downregulating SMAD2 to normal levels and potentially correcting pulmonary hypertension. Drugs for this treatment avenue have not yet been developed but were rather the ultimate goal of this group. We will stay alert for any new developments from this or other groups as early treatment trials are reported. Subsequently, we will be able to organize treatment trials to determine the effectiveness of these drugs in children with Trisomy 18. This report provided a glimmer of hope that there will be novel therapies on the horizon for helping children with Trisomy 18. When they are, we will be ready.
