Down Syndrome Regression Disorder: Not One-Size-Fits-All

For as much as we think we know about Down syndrome, there is still more and more that we are learning. In fact, we are sometimes explaining things to families at the same time we are learning them. Ten years ago, we taught that it was “inevitable” that adults with Down syndrome would get Alzheimer’s disease. Now we know that while it is more common at a younger age than in the general population, it is not inevitable. Many who are found to have Alzheimer’s features by MRI do not actually have symptoms. We are always learning! 

What Is Down Syndrome Regression Disorder?

Down syndrome regression disorder (DSRD) is now becoming a recognized as a new complication of Down syndrome. We had heard of one-off cases of young adults with Down syndrome who were doing well and suddenly stopped doing the things that they enjoyed before. Some were described as catatonic, some as withdrawn. In general, these changes seemed to come “out of the blue” but in some cases there were triggers like the death of someone close, an infection, or even sometimes graduating high school. In some cases, underlying medical issues presented as a behavioral change like low thyroid level, manifesting celiac disease or low blood count. Those with Down syndrome often internalize symptoms and behavioral changes are how tell us something is going on. 

How Does DSRD Present in Children?

Through the great work of many Down syndrome centers around the US, DSRD started to be recognized but it is still not a one-size-fits-all phenomenon. Everyone with Down syndrome has their own version of symptoms and their own version of response. 

Treating underlying medical issues such as by giving thyroid medicine, providing iron supplementation, and employing a gluten-free diet seems to help in many cases. As centers have recognized this, they continue to work on details. There are now some established criteria, but other causes must continue to be ruled out first. 

It appears as if the remainder of patients have some form of autoimmune disease. This is shown either as part of their work up which includes a lumbar puncture and retrieving cerebral spinal fluid (the fluid that surrounds the brain and some nerve tissues, also called CSF). 

In patients with autoimmune disease, evidence of more protein in CSF exists because immunoglobulins (antibody proteins) are seemingly causing the autoimmunity. But even in those with clear evidence of autoimmune disease, some patients will respond to treatment, an infusion of immunoglobulins by IV or stronger medical therapies to suppress immune function. This method also increases the risk for infections because the immune system is suppressed. The hope is that this treatment is only needed temporarily: patients with Down syndrome are at increased risk for autoimmune conditions and we have seen more evidence of DSRD in those already having one or more autoimmune conditions. 

Some patients have been helped by other treatments such as electroconvulsive shock therapy (not what is seen in the movies!) or transcranial magnetic stimulation, which stimulates nerve cells in the brain using magnetic fields. For some patients, this has been effective in the both the short term and long term.

We at Nationwide Children’s Hospital and Ohio State University are working together to create a more standard of care for DSRD workup and treatment.