What is NRXN1 Deletion Syndrome?

NRXN1 Deletion Syndrome occurs when all or part of the NRXN1 gene is missing, which prevents the gene from working as it should. This can lead to a range of developmental and psychiatric symptoms. No two people are affected in exactly the same way.

Symptoms experienced by individuals with NRXN1 Deletion Syndrome vary widely. Some individuals experience severe cognitive or psychiatric difficulties, while others experience few effects. In fact, some children inherit the deletion from a parent who is minimally affected, if at all.

Possible symptoms of NRXN1 Deletion Syndrome include:

  • Developmental delays in speech, motor, and/or cognitive skills

  • Intellectual disability or milder learning disorder

  • Autism spectrum disorder, or autistic features

  • Tic disorders, including Tourette syndrome

  • Seizures

  • Attention deficit/hyperactivity disorder (ADHD)

  • Schizophrenia

  • Other neuropsychiatric features (obsessive-compulsive disorder, bipolar disorder, anxiety, depression)

The good news is that no other major medical problems have been frequently associated with NRXN1 Deletion Syndrome. It seems that most individuals are physically healthy.

NRXN1 Gene and Chromosome 2p16.3 Deletion

NRXN1 is one of the largest genes in the human genome. It 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). Some genetic tests will report 2p16.3 deletion instead of NRXN1 deletion, but these are usually the same condition. Rarely, a person may have a larger deletion that includes additional genes beyond NRXN1. Most of the time, 2p16.3 deletions are “intragenic,” meaning they occur within the NRXN1 gene itself.

NRXN1 and the Synapse

The NRXN1 gene encodes the neurexin 1 protein, which is important for connecting neurons at the synapse.

Neurons are specialized cells in the brain. They communicate with one another through an action potential, which is an electrochemical signal. The synapse is the junction where a sending cell (presynaptic) communicates with the receiving cell (postsynaptic). Neurotransmitters are the chemical signals that are released at the synapse.

Neurexin 1 is a presynaptic cell adhesion protein, meaning it helps to align and connect the sending cell with the receiving cell. It does this by binding to specific post-synaptic proteins, much like a key fits into a lock. There are many binding partners of neurexin 1 depending on the type of synapse. Interestingly, variants in genes encoding for some of these postsynaptic binding partners, such as NLGN1 and NLGN2, are also associated with neurodevelopmental disorders.

When one copy of NRXN1 is not functioning properly, as is the case in NRXN1 disorder, neurotransmitter release and subsequent synaptic functioning is impaired.