Understanding Williams Syndrome
WIlliams syndrome is viewed by many scientists as a fascinating example of the link between genetics and our social brain function. Williams syndrome is a genetic disorder caused by the deletion of a portion of chromosome 7, affecting brain structure, cognitive function, and physical health. Individuals with this condition present with hypersociability, extreme friendliness, distinct facial features, and cardiovascular issues. In order to understand the origin of these symptoms and the variations that can occur, it is essential to trace them back to their genetic roots and underlying biological structures.
The Genetic Basis of Williams Syndrome
Williams syndrome occurs with the deletion of genetic material from a specific section of chromosome 7. This region consists of 25-27 genes each responsible for a different feature of the body. Depending on what genes in this region are deleted, different common symptoms of Williams syndrome can be experienced.
For example, the deletion of gene ELN on chromosome 7 causes a reduction in elastin production, which explains why many with Williams syndrome suffer from connective tissue abnormalities and cardiovascular disease. Deletion of gene LIMK1 is typical with Williams syndrome. This gene is an important component in the areas of the brain that process visual-spatial information, which is why many with the condition have a hard time with visual-spatial tasks like puzzles and drawing.
Although Williams syndrome is a genetic condition, it usually occurs due to a spontaneous mutation at conception rather than being inherited. However, if someone with Williams syndrome has a child, there is a 50% chance that the child will also have the genetic condition.
Diagnosing Williams Syndrome
Diagnosing Williams syndrome involves a combination of clinical observation and genetic testing. If a patient has identifiable features of Williams syndrome, they will be referred to genetic testing for a definitive diagnosis.
Clinical Diagnosis
A clinical diagnosis involves looking at a patient’s medical history, performing a physical examination and observing presenting symptoms and behaviors. People with Williams syndrome tend to have a smaller stature with characteristic facial features described as looking “elfin”. These features include a small chin, wide set eyes, a petite upturned nose, and a flattened nasal bridge.
Behaviors that can be observed include over-friendliness, hyper-sociability, perseverance on favorite topics, mild to moderate intellectual disability, a good vocabulary, and difficulties with visual-spatial tasks. Additionally, individuals with Williams syndrome often have a natural talent and enjoyment for music but may struggle with math and writing. A medical history suggestive of a Williams syndrome diagnosis may include gastrointestinal and cardiovascular issues, hypertension, connective tissue disorders, and heightened sensitivity to sound. It is important to note that even if a person has every single clinical feature of Williams syndrome, a definitive diagnosis cannot be achieved without genetic testing.
Genetic Testing
Genetic testing for Williams syndrome identifies specific DNA markers using a small amount of blood from the patient. Since 98–99% of individuals with the common features of Williams syndrome have a deletion of the elastin gene (ELN), it is considered the primary genetic marker for the condition. There are two genetic tests that patients can undergo to determine if they have Williams syndrome. These are the fluorescent in situ hybridization (FISH) test and the microarray.
FISH
The FISH test analyzes chromosomes using specialized elastin probes to determine the existence of the elastin gene. A person with both copies of ELN most likely does not have Williams syndrome, while someone who has only one copy is diagnosed with WS.
Microarray
The microarray is a more advanced genetic testing method than the FISH test and is the preferred approach for diagnosing Williams syndrome. This technology uses millions of genetic markers to analyze chromosomes in detail, identifying missing or extra genetic material anywhere in the genome. By providing a more comprehensive view of specific gene deletions, the Microarray test offers patients a clearer understanding of the unique characteristics of their condition.
Neurological and Cognitive Profile
Williams syndrome is an amazing example of how our genetics can shape our brain and behavior. Brain imaging technology reveals that individuals with WS have brains that are, on average, 15% smaller than typical, with distinct brain structure differences in areas responsible for spatial skills, decision-making, and social interactions.
Frontal and Temporal Lobes
Relative to the rest of the brain, the frontal and temporal lobes of those with Williams syndrome are usually normal in size, making them large in comparison to the rest of the brain. The planum temporale is a part of the temporal lobe that is thought to be involved in music, language, and auditory processing. The relatively normal to large size of the planum temporale in those with Williams syndrome can help to explain their talents with music and language.
Studies have found that the amygdala, another structure within the temporal lobe, functions differently in individuals with Williams syndrome. The amygdala is a key component of emotional processing and connects to areas of the brain involved with vision and hearing. In individuals with Williams syndrome, studies have observed increased amygdala volume and activity when viewing happy, friendly faces but a weaker, blunted response to fearful expressions. These amygdala responses are considered to be a contributing factor as to why individuals with Williams syndrome are hypersocial and extremely friendly yet fail to recognize and respond to more negative social cues.
Occipital and Parietal Lobes
The occipital and parietal lobes are located in the back of the brain and are responsible for processing visual, spatial, and sensory information. In individuals with Williams syndrome, these areas of the brain are noticeably affected with a significant reduction in volume. The reduced volume of these areas of the brain is linked to the poor visual-spatial abilities of those with Williams syndrome. Tasks requiring spatial reasoning, such as solving puzzles, drawing, and recognizing visual patterns, can be particularly challenging for them.
Connective Tissue and Cardiovascular Challenges
Over 97% of people with Willliams syndrome are missing the gene sequence ELN from chromosome 7. The gene sequence ELN codes for the creation of elastin in the body, a protein responsible for maintaining the elasticity and flexibility of tissues and organs. When someone is missing a copy of the ELN gene, the elastin in their body is thinner and does not function as it normally would, leading to differences in tissue elasticity and functionality.
Elastin is utilized in blood vessels and arteries, where it allows them to stretch and recoil, helping to regulate blood flow and maintain blood pressure. A deficiency in elastin causes blood vessels to become stiff and narrow, which can lead to multiple complications and heart failure. Supravalvular aortic stenosis (SVAS) is a narrowing of the aorta, the large blood vessel that carries blood from the heart and throughout the body. A narrowing of this blood vessel causes the heart to have to work harder to pump blood through the aorta, leading to shortness of breath, chest pain, and ultimately failure of the heart if left untreated.
The Future of Williams Syndrome
Williams syndrome is a powerful example of how genetics influence brain structure, cognition, and physical health. By understanding the genetic basis of the condition, researchers have uncovered the biological mechanisms behind its characteristic traits, from hypersociability to cardiovascular complications. Advances in genetic testing and neuroimaging continue to provide deeper insights into how Williams syndrome affects individuals at a molecular and neurological level. While challenges exist, early diagnosis, medical management, and tailored support can help those with Williams syndrome lead fulfilling lives. Ongoing research remains essential to furthering our understanding and improving outcomes for individuals with this rare genetic condition.
Learn more about what it’s like to live with Williams syndrome Here