Understanding Noonan Syndrome
This past November the mug shot of Charles McDowell went viral after viewers noticed that the man in the photo had an unusual phenotype- specifically a larger than average neck. In the comments section thousands of people went wild making neck puns and neck memes. Soon after this internet craze took hold a second voice emerged. Sarah Adams, a Noonan Syndrome (NS) activist and mother of a late Noonan Syndrome patient, took to Facebook to raise awareness that what seemed like innocent fun could very well be making fun of a genetic disability.
Noonan Syndrome (NS) is a genetic disorder associated with several distinct features. The physical characteristics associated with NS include a broad, webbed neck, heart defects, a short stature, pubertal delay, deformity of the sternum, bleeding disorders, and characteristic facial features. It affects roughly 1 in 1,000 to 1 in 2,500 people, making NS one of the most common genetic disorders.
“NS is a ‘RASopathy,’ meaning it is a genetic disorder that disrupts a signaling pathway regulated by an enzyme called Ras.”
NS can also be associated with neurological phenotypes. Between 30% to 50% of patients show cognitive deficits. Learning disabilities, motor development delays, speech and language pathology, and sometimes more serious complications like severe neurodevelopmental disorders are associated with NS.
What do we know about how NS affects the brain? NS is a “RASopathy,” meaning it is a genetic disorder that disrupts a signaling pathway regulated by an enzyme called Ras. Ras is a molecule that turns this signaling pathway back off once it has been activated. This communication breakdown overactivates excitatory neurons (neurons that make other neurons more likely to fire).
What causes Ras to go awry? The most common cause of NS is a mutation in a gene called PTPN11. This mutation results in a loss of functional protein from the gene, causing a receptor directly upstream on Ras to be overactive. PTPN11 is a “phosphatase,” which is a kind of enzyme that turns off other proteins once they have been activated by enzymes called “kinases.” When kinase activity isn’t balanced out by phosphatase activity, such as by a loss of PTPN11, this leads to overactivation of the downstream signaling pathway.
“McDowell has successfully parlayed the internet humor into Instagram stardom.”
In animals that are genetically engineered to show symptoms of NS, heterozygous mutations in PTPN11 (i.e., mutations occurring from only the mother or the father’s copy of the gene) cause deficits in long-term potentiation (the ability of neurons to strengthen their connections) and learning impairments. Alcino Silva, a neuroscientist at UCLA, has shown in his lab that pharmacologically decreasing this excitatory signaling can rescue cognitive deficits. Studies to determine whether this mechanism will help human patients are currently being carried out by the pharmaceutical company Novartis.
McDowell has successfully parlayed the internet humor into Instagram stardom, accruing 590k followers since his first post on November 26th. Although we can’t say for sure whether he is a NS patient, we do know that people who are predisposed to intellectual disability are more likely to get caught up in the criminal justice system. In the general population 2% to 3% of people have an intellectual disability, whereas the prevalence rises to 4% to 10% for the prison population. These numbers are even higher among incarcerated juveniles.
Although McDowell seems to be enjoying his newfound internet fame, this potential link between a disability and a physical phenotype falls in to a larger pattern of discrimination against people with disabilities. According to one study 60% of people with disabilities experience regular bullying, compared to 25% of non-disabled people. A first step toward ending disability-based harassment can be to become curious about differences. Getting informed about a disability, as well as speaking up and informing others, can create a fundamental shift in how we perceive disability as a society.
Can you think of other phenotypes associated with genetic conditions? Tell us in the comments below!
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References
Know Your Meme. (2018). Charles McDowell’s Large Neck Mugshot. Retrieved from: https://knowyourmeme.com/memes/charles-mcdowells-large-neck-mugshot
Bhambhani, V., & Muenke, M. (2014). Noonan Syndrome. American Family Physician, 89(1), 37–43.
Lee, Y.S., Ehninger, D., Zhou, M., Oh, J.Y., Kang, M., Kwak, C.,… Silva, A.J. (2014). Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome.Nature Neuroscience, 17(12), 1736-43.
Davis, L.A. (2009). People with Intellectual Disability in the Criminal Justice System: Victims & Suspects. The Arc. Retrieved from: https://www.thearc.org/what-we-do/resources/fact-sheets/criminal-justice
PACER Center. (2018). Bullying and Harassment of Students with Disabilities. Retrieved from: https://www.pacer.org/bullying/resources/students-with-disabilities/
it’s first time to know about this syndrome, thanks for sharing