Up till now, I haven’t felt too comfortable mentioning what type of chromosome mutation CB has. I guess it has just taken some time to absorb the information, and partly lack thereof, and to feel more comfortable about discussing it in such an open forum. I also feel that it is important for me to be able to discuss our journey and to release my thoughts but I also want to be able to protect my son. It will be awhile before he will understand what this blog means and its impact. Heck, I am not fully aware of its impact. This all goes back to one of my first blogs about what right I have as a parent to share my child’s journey even though he is not an age where he can comprehend social media and its far-reaching effects. Despite all of this, I want to put it out there as it would be great to potentially connect with other families who might have children with the same genetic condition.
My son’s genetic condition is a loss-of-function of the SETBP1 gene, otherwise stated as a SETBP1-related disorder based off the document provided by my son’s geneticist. The gene is located on the long arm (referred to as q) of Chromosome 18 closer to the centromere than the end of the chromosome (proximal). There is a recognized genetic condition that is caused by a deletion within/of the SETBP1 gene and/or other genes in a similar location on Chromosome 18 and the condition is called Proximal Chromosome 18 Deletion Syndrome or 18q- for short. My son’s genetic difference is de novo (meaning neither my husband or myself have this same genetic difference), autosomal dominant (if my son has children, they will have a 50% chance of having the same genetic difference) and the difference is heterozygous (which means he expresses 2 difference forms of the gene). The genetic variant is pathogenic so it is understood to impact the function of the gene and to impact the child’s overall function. It is important to understand whether the difference is due to a loss-of-function (producing less than the normal amount of the protein/gene) or a gain-of-function (producing more than the normal amount of the protein/gene) as the overall difference is very different. I talked a littler further about getting the initial results and a bit more about the details in an earlier blog, Whole Exome Sequencing Genetic Results.
There has been a study that defined a phenotype for children with a loss-of-function of the SETBP1 protein/gene. The details of the study can be found in the article titled Refining analyses of copy number variation identifies specific genes associated with developmental delay The study includes 13 individuals with this genetic difference, as well as, many others with other genetic differences. All children in the study had a speech delay or absent speech, and most had intellectual disabilities, motor delays, and some degree of facial dysmorphism. About half had hyperactive/ADHD, social difficulties and other behavioral difficulties. Just under half had seizures or EEG abnormalities. The ages ranged from 4-73 years old with 9 of the subjects being male.
You can find out more about Proximal 18q- at the Chromosome 18 Registry and Research Society’s website at http://www.chromosome18.org/18q/proximal-18q/ and at Unique’s website at http://rarechromo.org.