Fragmented chromosome 22 slowly piecing itself back together amidst a backdrop of abstract neural networks and glowing synapses.

22q11 Deletion Syndrome: Unlocking the Mystery of Psychosis Vulnerability

Lena Kashyap in Health & Wellness December 2025 • 4 min read.

"Is there a link between this genetic anomaly and increased risk? Neurological soft signs reveal potential insights."

The 22q11 microdeletion syndrome (22q11DS), also known as velo-cardio-facial syndrome or Di George Syndrome, is a neurogenetic disorder impacting roughly 1 in every 4,000 live births. This condition arises from a missing piece of chromosome 22 and is a multisystemic disorder, leading to a wide range of congenital issues from facial differences and heart defects to immune deficiencies.

Adding to the complexity, 22q11DS is often associated with neurocognitive challenges, including intellectual disabilities, learning differences (particularly in math), and difficulties with visuospatial skills, attention, and executive functions. Moreover, a significant number of individuals with 22q11DS experience psychiatric disorders, most notably attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder, anxiety, mood disorders, and schizophrenia spectrum disorders. Compared to the general population, those with 22q11DS face a dramatically increased risk of psychosis.

Given these factors, recent research has investigated a potential connection between ‘neurological soft signs’ (NSSs) and 22q11DS. Neurological soft signs are subtle motor, sensory, or integrative abnormalities that, while not indicative of specific brain lesions, may point to broader neurodevelopmental differences. Studies suggest that these signs could act as markers of vulnerability to schizophrenia. Thus, exploring the presence and nature of NSS in individuals with 22q11DS could further our understanding of the syndrome’s link to psychosis.

Neurological Soft Signs: What Do They Tell Us?

Fragmented chromosome 22 slowly piecing itself back together amidst a backdrop of abstract neural networks and glowing synapses.

Neurological soft signs (NSS) encompass minor motor, sensory, and coordination-related features that don't fit neatly into specific diagnostic boxes but can indicate underlying neurological differences. Common NSS include:

Considered as subtle indicators of brain function and development, NSS can include slight impairments in motor coordination, sensory integration, and sequencing complex motor tasks. While individually minor, their presence in clusters can signify broader neurological vulnerabilities.

Overflow Movements: Involuntary movements in body parts not directly involved in a task.
Dysrhythmia: Irregularities in the rhythm or timing of movements.
Difficulties with Timed Activities: Challenges in performing tasks within a specific time frame, such as rapidly alternating hand movements.

Researchers have observed that individuals experiencing a first psychotic episode tend to exhibit a greater number of NSS compared to the general population. Furthermore, about 60% of people diagnosed with schizophrenia present with NSS. Given these observations, NSS are believed to be an endophenotype (a measurable component unseen by the naked eye that relates to genes) for psychotic disorders. The study aims to fill a critical research gap by measuring neurological soft signs in patients with 22q11DS and those at ultra-high risk for psychosis, comparing them to healthy controls. It also explores correlations between neurological soft signs and both positive and negative symptoms in the two clinical groups.

Implications and Future Directions

This research highlights the significance of neurological soft signs as potential markers of atypical neurodevelopment in individuals with 22q11DS and those at ultra-high risk for psychosis. While NSS do not appear to directly correlate with specific positive or negative symptoms, their presence may indicate an underlying vulnerability to psychosis independent of psychopathology. Longitudinal studies with larger samples are needed to fully understand the predictive value of NSS and to clarify their relationship with specific brain circuits.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1111/eip.12754, Alternate LINK

Title: 22Q11 Microdeletion Syndrome And Ultra‐High Risk For Psychosis: The Role Of Neurological Soft Signs As An Independent Marker Of Vulnerability For Psychosis

Subject: Biological Psychiatry

Journal: Early Intervention in Psychiatry

Publisher: Wiley

Authors: Mariabernarda Pitzianti, Maria Pontillo, Stefano Vicari, Marco Armando, Augusto Pasini

Published: 2018-11-26

Everything You Need To Know

What is 22q11 microdeletion syndrome, and why is it important to study?

The 22q11 microdeletion syndrome, also known as velo-cardio-facial syndrome or Di George Syndrome, is a neurogenetic disorder caused by a missing piece of chromosome 22. This can lead to various congenital issues, such as facial differences, heart defects, and immune deficiencies. It is significant because it's associated with neurocognitive challenges like intellectual disabilities, learning differences, and psychiatric disorders. It also increases the risk of psychosis compared to the general population. Understanding this syndrome is crucial for early detection and support for those affected.

What are neurological soft signs, and why are they significant in understanding psychosis?

Neurological soft signs (NSS) are subtle motor, sensory, or integrative abnormalities that may indicate broader neurodevelopmental differences. Examples include overflow movements (involuntary movements in unrelated body parts), dysrhythmia (irregular timing of movements), and difficulties with timed activities. NSS are important because they are believed to be an endophenotype for psychotic disorders, suggesting a potential link between these signs and the underlying genetic or neurological vulnerabilities to psychosis.

What is the aim of the study?

The study measures neurological soft signs in patients with 22q11DS and those at ultra-high risk for psychosis, comparing them to healthy controls. The study also explores correlations between neurological soft signs and both positive and negative symptoms in the two clinical groups.The study found that the presence of NSS may indicate an underlying vulnerability to psychosis independent of psychopathology. This research highlights the importance of neurological soft signs as potential markers of atypical neurodevelopment in individuals with 22q11DS and those at ultra-high risk for psychosis. More research needs to be done to fully understand the predictive value of NSS.

Does having 22q11 deletion syndrome guarantee that someone will develop psychosis?

While research indicates that individuals with 22q11DS have an increased risk of psychosis, the exact mechanisms are still being investigated. Neurological soft signs (NSS) are being explored as potential markers of vulnerability. The presence of NSS may suggest an underlying neurological vulnerability that contributes to the increased risk. However, it's essential to understand that not everyone with 22q11DS will develop psychosis, and the relationship is complex and requires further study.

What future research is needed?

Future research should include longitudinal studies with larger samples to fully understand the predictive value of neurological soft signs (NSS) and to clarify their relationship with specific brain circuits. It's important to investigate how NSS might interact with other genetic and environmental factors to influence the development of psychosis in individuals with 22q11DS. Additionally, more targeted interventions and support strategies can be developed based on a deeper understanding of these relationships.