How do you pronounce “NRXN1” and “2p16.3 deletion”?

NRXN1: “neurexin one”. 2p16.3: “2p one six point three”

What’s the difference between NRXN1 deletion and 2p16.3 deletion?

They’re the same thing. NRXN1 is one of the largest genes in the human genome, so deletions can occur within the gene itself but still be rather large. NRXN1 is located at position “16.3” on the short arm (p) of chromosome 2 (in other words, 2p16.3 is the “address” of the NRXN1 gene). Rarely, a person may have a larger deletion that includes additional genes beyond NRXN1; however, most of the time 2p16.3 deletions are “intragenic,” meaning they occur within the NRXN1 gene itself.

What’s the difference between 2p16.3 deletion and 2p16.3 microdeletion?

They’re the same thing. Before modern genetic testing technology, there used to be a distinction between deletions that were large enough to see under a microscope and those that were not. This distinction is no longer relevant, as the technology has changed and most deletions are now detected through microarray or exome sequencing with copy number variant detection.

Does the size of a person’s deletion correlate with the severity of their symptoms?

Not necessarily; what’s more important is the location as well as the impact of the deletion itself. Very small deletions that occur within the coding portion of the gene, called the exon, may effectively “turn off” the gene’s ability to function and have the same effect as a much larger deletion. These types of deletions are called “loss of function.” Deletions that do not impact the coding portion of the gene but are instead located in the non-coding portion of the gene (the intron) may not have a significant effect on the gene’s ability to function.

What if a person has a deletion of NRXN1 on both copies of their chromosome?

Genes come in pairs. Individuals who have two non-working copies of the NRXN1 gene have a more severe condition called “Pitt-Hopkins-like syndrome 2.” Most individuals with this condition have severe to profound intellectual disability, absent speech, severe epilepsy, and breathing difficulties.

If I have multiple children with NRXN1 deletions, does that mean that I or their other parent definitely has the same deletion?

In all likelihood, yes, that means that each child inherited it from a parent. However, there is a small chance that neither parent has NRXN1 deletion themselves but may carry egg or sperm cells only with the deletion (called germline mosaicism, or gonadal mosaicism).

If I have one child with NRXN1 disorder, what are my chances that I could have another child with the same disorder?

This depends on whether you or the other parent was found to have a NRXN1 deletion. If one parent has a NRXN1 deletion, the chances of having a child with the same deletion would be 50%. If neither parent has the deletion, the child’s deletion would be considered “de novo” and the chances of having another child with the same deletion would be very small (but not 0 due to possible germline mosaicism).

Are there any specific treatments for NRXN1 Deletion Syndrome?

Unfortunately, there are no cures or treatments that specifically target NRXN1. Because each person with NRXN1 deletion has different symptoms, it’s important to target that individual person’s symptoms. For instance, if a child has anxiety then cognitive behavioral therapy and/or anxiety medications might be helpful. Alternatively, if a child has ADHD then stimulant medications may be effective. Individuals with speech disorders may respond well to speech therapy.

Are there medications that have been found to work better with individuals with NRXN1 Deletion Syndrome?

To my knowledge, there has been no research into specific medications that work better or worse for individuals with NRXN1 deletion. There is also no evidence that specific medications would be contraindicated, although each person’s health is unique and they should always consult with a physician before starting medications (prescription, over the counter, supplements).

There has been one study in mice (not people) with knocked-out Nrxn1a that showed some benefit of ketamine in restoring connectivity in the thalamus and affected parts of the mouse brain (Hughes et al, 2020); however, much more research is needed in the area before such a treatment could be recommended in humans.

My child and I both have the same NRXN1 deletion. Why does my child have developmental delays but I don’t have any symptoms?

Scientists don’t know for sure, but we often see this phenomenon in genes associated with neurodevelopmental and neuropsychiatric disorders. This is called “incomplete penetrance” and “variable expressivity,” which means that the way the deletion affects one person may be very different from how it affects another. In all likelihood, a combination of factors are at play, including a person’s genetic background, external factors (such as prematurity or serious illness), as well as pure chance in how babies grow in the womb. Some studies have found that a subset of children with NRXN1 deletions have a second gene change (or “second hit”), and the combination of gene changes are thought to compound the neurodevelopmental effects observed.

What does the future hold for my child?

The good news is that there isn’t evidence that NRXN1 disorders put children at risk for serious health effects later on. There is no reason to think that children’s lifespan would be shortened. We do know that individuals with NRXN1 deletions are at risk for developing serious mental illness later in life (such as schizophrenia, OCD, severe anxiety/depression), although this develops in a minority of individuals. Caregivers should be attuned to behavior changes and be proactive in getting their children help if they suspect they are developing emotional difficulties or thought disorders.

What can my family do to raise awareness and improve treatments for people with NRXN1 Deletion Syndrome?

Check out the links under “Get Involved” for ways to help! These include donating, volunteering, sharing your story, participating in research, and shopping at our store.

In particular, there is so much we don’t know about NRXN1 Deletion Syndrome The only way to learn more is to partner with researchers and volunteer for research studies.