What is Williams Syndrome?
Williams syndrome (WS) is an uncommon disorder that affects a person’s genes and brain development. It usually becomes apparent at birth when the baby is found to have a condition called supra-vascular aortic stenosis, which is a narrowing of the large blood vessel branching off the heart. The baby also displays unique facial features that resemble those of elves (described as “elfin-like features”), as well as other signs such as an overly friendly personality, intellectual disability, growth abnormalities, behavior deficits, and issues with their connective tissues and calcium levels.
The syndrome got its name from Dr. John Cyprian Phipps Williams, a cardiologist who first identified it in 1961. In 1962, Dr. A. J. Beuren made similar observations, leading to the syndrome also being referred to as Williams-Beuren syndrome.
What Causes Williams Syndrome?
Williams syndrome, a medical condition, was found to have a genetic origin in 1993. The syndrome is caused by a missing segment on a specific part of chromosome 7, which normally contains the elastin gene (ELN). This gene is present in the so-called Williams-Beuren Syndrome Critical Region (WBSCR).
The missing section typically comprises around 26 genes. This can be identified through tests called dual-color fluorescent in situ hybridization (FISH) or deletion/duplication testing, which can detect if part of the genetic material is missing or duplicated. Another test, called a microarray analysis, can determine the size of the missing elastin.
For these tests, a blood sample is taken from the patient, and DNA is extracted for study. According to the findings, between 96 to 98% of patients with Williams syndrome are missing the elastin gene. This genetic disorder is passed down in an autosomal dominant manner, meaning only one copy of the altered gene in each cell is sufficient to cause the disorder.
The absence of elastin can lead to widespread arterial disease, which can affect any artery in the body, but it most commonly affects medium to large-sized arteries.
Risk Factors and Frequency for Williams Syndrome
Research shows that the disorder is estimated to affect between 1 in 7,500 and 1 in 75,000 children. It’s important to note that this disease does not discriminate – it affects all ethnicities and both boys and girls equally.
Signs and Symptoms of Williams Syndrome
After birth, babies with a condition called Williams Syndrome often have trouble growing, are shorter than others their age, and can have heart problems such as supra-vascular aortic stenosis. This is because they have a problem with their elastin, a protein that makes their blood vessels flexible. This can lead to other heart and lung complications like peripheral lung stenosis and high blood pressure.
These children often have ear infections and vision problems as they grow. They also have unique facial features that make them look as though they have an elfin-like appearance.
Continuing on, young ones with Williams Syndrome often have problems with their hormones. This can cause high calcium levels in their blood and urine, which may lead to kidney stones. Some other signs can include low thyroid levels, lagging growth, or puberty coming on too early.
Another complication of Williams syndrome is problems with connective tissues. This could lead to very flexible joints or low muscle tension, causing delays in reaching milestones like walking, and toilet-training.
Those children with Williams Syndrome who have blue or green eyes often have a pattern in their iris that looks like a starburst. This starburst pattern makes the eye appear white and lacy.
Along with the physical symptoms, children may also have mental health conditions like intellectual disability, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and generalized anxiety disorder.
Finally, to be sure a child has Williams syndrome, doctors will use a type of genetic test called FISH. This test will look to see if a specific piece of the child’s genes is missing.
Testing for Williams Syndrome
If your doctor suspects you might have Williams syndrome, a variety of tests might be ordered to confirm this. These may include measuring your body mass index (BMI), which tells us if your weight is healthy for your height, a complete blood count (CBC) and a complete metabolic panel (CMP) to check your overall health, and a test for calcium levels since this can be high in Williams syndrome. You might also be tested for thyroid stimulating hormone (TSH), including free T3 and free T4, since this can impact your metabolism.
Beyond blood tests, your doctor might also check your hearing and vision, as these can be affected in Williams syndrome. Furthermore, an echocardiogram (an ultrasound of the heart) and an electrocardiogram (ECG, a test that checks your heart’s electrical activity) might be performed, as heart problems are often associated with this condition.
Williams syndrome often comes with intellectual disability (ID), which can be assessed using a test called the Kaufman Brief Intelligence Test, Second Edition (KBIT-2). This test measures a person’s general intelligence and provides scores related to verbal and non-verbal abilities. Studies have found that children with Williams syndrome can range from average intelligence to severe intellectual disability.
However, the KBIT-2 does not measure the ability to perform tasks involving vision and spatial relationships, often known as visuospatial construction, an area where many children with Williams syndrome may struggle. To measure this ability, your doctor might use tools like the Differential Ability Scale-II (DAS-II), a test meant to evaluate a range of cognitive abilities, or Wechsler IQ tests.
Treatment Options for Williams Syndrome
To effectively treat and manage children with Williams Syndrome (WS), a syndrome that affects many parts of the body and is characterized by medical problems like cardiovascular disease, developmental delays, and learning challenges, a team of various healthcare professionals is needed.
Firstly, upon diagnosis, genetic counseling is recommended. Genetic counseling helps to understand the cause of the syndrome and what to expect.
Pregnancies in patients with WS are considered high risk due to possible complications like irregular heart rhythms, heart failure, and high blood pressure. Therefore, all pregnant women with WS receive special attention from the obstetrics department. This might include routine ultrasound scans of the baby, urinalysis to check for urinary tract infections, and prenatal testing.
Upon birth, children with WS often require the attention of cardiologists because they might have a condition called supra-vascular aortic stenosis, which affects the heart’s aorta. In some cases, this may necessitate open-heart surgery. After this surgery, the cardiologists continue to monitor the patients closely due to the risk of high blood pressure and various forms of arteriopathy – the disease of the blood vessels.
Endocrinologists also play a crucial part in managing WS, as children with WS often experience hypercalcemia (high calcium levels in the blood), hypothyroidism (an underactive thyroid gland), and growth restrictions. Thus, the children might need a special diet to control their calcium levels and avoid kidney issues, regular monitoring of their glucose and thyroid function, possible hormone replacement therapy, and possibly even the use of growth hormone to stimulate growth.
If kidney stones develop due to high levels of calcium in the urine, nephrologists might be needed to treat them. For children experiencing difficulties in feeding, a referral to gastroenterologists might be necessary because in some cases, a permanent feeding tube might be required. For this reason, consultation with a nutritionist can be helpful.
Psychiatrists can also be valuable to evaluate the need for medications or psychotherapy to treat concurrent conditions like ADHD, OCD, or Generalized Anxiety Disorder.
Given the potential for intellectual disability and development deficits in patients with WS, the children might also need to be enrolled in special education programs or receive additional support like occupational therapy, physical therapy, or speech therapy.
Because kids with WS are at risk of vision problems and recurrent ear infections, they need regular checks for sight and hearing impairments.
Since WS can also cause dental abnormalities, regular visits to a dentist or an orthodontist are also recommended.
What else can Williams Syndrome be?
When trying to diagnose Williams Syndrome (WS), it’s very important to consider and rule out other conditions that have similar symptoms. These include:
- Fetal alcohol syndrome
- DiGeorge syndrome (deletion 22q11.2)
- Noonan syndrome
- Smith-Magenesis syndrome
- Kabuki syndrome
- Marshall syndrome
There’s also a separate condition called “Autosomal dominant supra-valvular aortic stenosis” that needs to be ruled out, because it’s not the same as WS.
What to expect with Williams Syndrome
The health issues related to Williams Syndrome (WS) are primarily due to problems with the arteries and congenital (present at birth) heart diseases. Roughly 80% of people with WS have abnormalities in their cardiovascular system, such as narrowed large arteries or heart chambers, which often require heart surgery. During this surgical period, there’s a risk of sudden, severe cardiovascular failure that could lead to other health problems and even death.
In terms of inheritance, if a parent has WS, there is a 50% chance they could pass the gene alteration causing WS to their children. However, if a parent has a child with WS but the parent themselves does not have the syndrome, the chances of another child getting WS are pretty low.
People with WS usually can live either semi-independently or independently and are often capable of holding a job. As everyone with WS has different requirements, it’s advised to create a personalized life transition plan, ideally before the age of 13 or 14. This way, they’re better prepared for the transition to adulthood and independent living.
Possible Complications When Diagnosed with Williams Syndrome
Patients with Williams Syndrome (WS) who undergo open-heart surgery may face several complications. These risks often increase due to a problem with their elastin, a protein vital for skin and artery flexibility. A study tracked WS patients who had surgery related to problems in the right or left ventricular outflow tracts or supra-valvular aortic stenosis, which are parts of the heart that deal with blood flow from the heart to the body.
The study found that 9% of WS patients having open-heart surgery encountered major heart problems, including arrhythmia (abnormal heart rhythms) or coronary artery disease (blocked heart arteries). For those who develop blocked arteries after surgery, they may need a procedure called revascularization to restore the blood flow.
Key Risks:
- Increased complications due to elastin deficiency
- Major heart problems (like arrhythmia or coronary artery disease)
- Possible need for revascularization after surgery
Preventing Williams Syndrome
If you or your loved ones have any questions about the condition, don’t hesitate to ask your healthcare team. They are there to help you understand and manage the situation. For more details about the disorder, you can also visit the Williams Syndrome Association’s website at williams-syndrome.org.
