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Rare genetic condition reshapes social behavior
A genetic disorder known as Williams Syndrome (WS) causes individuals to treat strangers with extraordinary warmth and trust, offering scientists new insights into the biological roots of human sociability and caution.
What is Williams Syndrome?
WS affects roughly one in 7,500 people worldwide. Those with the condition often exhibit high levels of empathy, talkativeness, and an innate desire to connect with others-traits that have led some researchers to describe it as the "opposite of autism."
However, this extreme openness comes with risks. People with WS frequently struggle to maintain long-term friendships and are vulnerable to exploitation due to their inability to recognize potential threats from strangers.
"They give themselves to anybody without prejudice, which seems like a lovely trait, but there's a reason human brains evolved to be cautious of new people. You don't know if they intend harm or kindness, and individuals with WS can't distinguish between the two."
Alysson Muotri, Professor of Pediatrics, UC San Diego
Genetic roots of the condition
WS occurs when a segment of chromosome seven is accidentally deleted during genetic recombination, removing 25-27 genes. This deletion disrupts critical functions, including the production of elastin-a protein essential for tissue flexibility-which contributes to lifelong cardiovascular issues.
Another affected gene, BAZ1B, influences neural-crest cells, which develop into facial structures and adrenal glands. This may explain the distinct facial features of people with WS, such as a small upturned nose and wide mouth, as well as their reduced fear response.
The science behind extreme sociability
Researchers have linked the gene GTF2I to the heightened friendliness seen in WS. Studies show that animals lacking this gene-including mice, fruit flies, and even dogs-display increased social behavior. Conversely, individuals with an extra copy of GTF2I often develop autism-like traits, including social anxiety.
Boaz Barak, an associate professor at Tel Aviv University, found that mice without GTF2I had reduced myelin-a fatty layer that insulates nerve fibers-impairing communication between brain regions responsible for fear and decision-making.
"When GTF2I is missing, myelination weakens, disrupting the connection between the amygdala (which processes fear) and the frontal cortex (which governs social decisions)."
Boaz Barak, Tel Aviv University
Barak's team is now testing clemastine, an allergy medication known to improve myelination, in a Phase 1 clinical trial for WS, with results expected by December 2025.
Oxytocin, synapses, and the brain's reward system
Some scientists propose that WS may also involve elevated oxytocin levels-the hormone associated with bonding. People with WS produce more oxytocin and have more receptors for it, potentially amplifying their feelings of trust and affection.
Alysson Muotri's research suggests another mechanism: an overabundance of synaptic connections in the brain. In 2016, his team grew neurons from stem cells donated by children with WS and found they formed more branches and connections than typical neurons.
"People with WS may experience a dopamine surge when meeting new people, creating an immediate sense of reward. Their brains might be wired to associate novelty with pleasure."
Alysson Muotri
In contrast, mini-brains derived from autistic individuals showed fewer connections, highlighting GTF2I's role in regulating social behavior.
Evolutionary implications
WS provides a window into how human social traits evolved. While extreme trust can be risky, a moderate level of sociability is vital for cooperation-a cornerstone of human survival.
"Evolution has fine-tuned GTF2I to strike a balance: too much friendliness is dangerous, but too little hinders social bonds. The gene's expression is calibrated to the 'right' amount of socialization."
Alysson Muotri
Health challenges and future treatments
Beyond social traits, WS is associated with cardiovascular disease, developmental delays, anxiety, and learning disabilities. Many individuals require lifelong support, though some live semi-independently.
Barak emphasizes that while WS traits like warmth and openness are valuable, treatments like clemastine could help those who struggle with the condition's downsides.
"We're not trying to 'fix' their behavior. Many families cherish their loved one's capacity for love. But for those who want it, existing drugs might offer relief from some challenges."
Boaz Barak
Research also suggests mitochondrial dysfunction in WS neurons, which may impair energy production and contribute to cognitive difficulties.
Key takeaways
- WS results from a deletion on chromosome seven, affecting genes like ELN (cardiovascular health) and BAZ1B (facial/neural development).
- The gene GTF2I appears central to sociability, with its absence linked to reduced fear and increased trust.
- Myelination deficits, oxytocin levels, and synaptic overconnectivity may all play roles in WS behavior.
- Ongoing trials aim to repurpose existing drugs to address WS symptoms without altering core traits.
