In Phelan-McDermid syndrome, you are likely familiar with the terminology and differences between SHANK3 deletions, SHANK3 variations, and even ring chromosomes. But what about Class I and Class II deletions? Recent clinical trials, including Jaguar Gene Therapy, have been using Class I vs. Class II deletions as inclusion/exclusion criteria. Because of this relatively newer terminology, we want to make sure our community understands the difference!
- Class I deletions: Smaller deletions including only SHANK3 or SHANK3 in combination with ARSA and/or ACR and RABL2B
- Class II deletions: All other deletions that did not qualify as Class I deletions, or in other words, larger deletions beyond SHANK3 and ARSA
We created this helpful diagram to help make this clearer!
What else do we know about the differences between Class I vs. Class II deletions?
So far, little is known about the clinical phenotype differences between Class I vs Class II. However, some evidence suggests that in individuals with Class II deletions, developmental delays are more common, cognitive and language impairments tend to be more severe, and there is a higher risk of medical coexisting conditions. In individuals with Class I deletions, psychiatric features are more common. However, we know there is a lot of variability in these findings and more studies are needed to clarify these differences.
Check out the following publication link for more information: