Williams syndrome is diagnosed by identifying that the person has only one copy of a gene called elastin. As the name indicates, elastin is a fiber made for stretching. Your body has many places where this elastin is important for an organ to function, but none as important as your blood vessels.
Blood Pressure
When you get down to the niddy griddy of the cardiovascular system, the heart and blood vessels really are just a series of roadways that lead the blood to and from important places throughout the body. Elastin is essential in the proper functioning of those "roadways". As the blood moves out of the large and spacious chambers of the heart and into the major artery, called the aorta, there is quite a large pressure change. Think of it like you are cruising along at a fast steady pace in rush hour on a six lane highway (the heart's left ventricle) and then the lanes take an abrupt merge into about 4 lanes; traffic backs up. This is what happens when blood goes through a doorway called the semilunar valve and into the aorta. The body relies on this pressure to give the blood movement. If you had no pressure, the blood would never be able to reach your toes and return against gravity, back to your heart. So, this type of traffic jam is a good thing.
Now, this is where elastin comes in. Your body works under a fascinating principle called homeostasis. You have to control your blood pressure so that it's not too great nor too weak, it needs a happy medium. This is where elastin comes in handy. When the pressure is too great in a blood vessel, the body can stretch the walls of the arteries outwards and create a larger space. This stretch is monitored by the body to create the perfect balance of pressure, or homeostasis. This stretch is possible because of the elastin in the vessel walls.
Photo courtesy of US Dept of Health and Human Services
Difficulty in maintaining the proper stretch in the blood vessels can lead to high blood pressure, also known as hypertension. Hypertension is an issue for about 50% of individuals with WS and can become an issue at any point in their lives.
Supravalvular aortic stenosis (SVAS)
Because individuals with Williams syndrome are missing an elastin gene on one of their chromosome pairs, they make less of it in their bodies. This causes a condition called stenosis. Stenosis basically means that that vessels in the body are narrow. So, take that bottle neck in the highway, remember, where you are going from 6 lanes to 4 and assume that the highway is narrower than average so now your going from 6 lanes to 3 or 2 or even 1. This is all determined by how severe the stenosis is.
The most common place we find stenosis in individuals with WS is just above the opening from the heart into the aorta. Remember that the aorta is the major artery that leaves the left side of the heart and delivers the body its oxygenated blood. When the blood moves out of the left ventricle (a chamber) of the heart it gets squeezed with much force and pushed through a valve. A valve is like a one-way door that opens into the aorta and lets blood in but closes behind it and keeps blood from moving backwards. The valve in this section of the aorta is called the aortic semi-lunar valve. Once the blood moves through the valve it enters the large muscle-lined artery of the aorta. The aorta then branches as it travels through the body to deliver the blood.
In Williams syndrome, stenosis is most likely to occur just above that doorway. This is called supra (super = above) valvular (that doorway) aortic (in the aorta) stenosis (narrowing). So, essentially, 75% of individuals with WS have a pinched section of aorta just above the valve. This is why the health of the heart and blood pressure are important to monitor in individuals with WS. They have to work harder to keep that happy balance of pressure with all the "traffic" problems this presents.
Other types of stenosis
With the lack of elastin in the body it's safe to assume that stenosis could occur in other places as well. Many parents are first warned of pulmonary stenosis. The pulmonary arteries carry blood from the right ventricle to the lungs so the blood can drop off carbon dioxide and pick up the much needed oxygen. Stenosis here can cause blood to back up on the right side and put strain on the heart. There are two types of pulmonary stenosis. 50% of the time it occurs in the arteries close to the lungs which are much smaller than the arteries closer to the heart. This is called peripheral pulmonary stenosis or PPS. PPS is often only an issue in infants and most will "grow out of it". As the baby grows, so will their pulmonary arteries. Pulmonary stenosis also occurs 25% of the time in the pulmonary trunk, just above the valve. The pulmonary trunk is a lot like the aorta, except it's on the opposite side of the heart and delivers blood to the lungs. It exits the right side of the heart and has a valve, or doorway that keeps the blood flowing in the right direction. The stenosis will occur just above that valve and is called supravalvular pulmonary stenosis or SVPS. This condition, like SVAS is a life-long health concern.
A second area of concern are the coronary arteries. These arteries lie on the surface of the front of the heart and deliver blood to the heart muscle itself. This muscle requires a great deal of sugars and oxygen to function and the narrowing of these arteries can cause heart failure. There is interest in the medical and research worlds about some individuals with WS who have dangerous reactions to anesthesia. There is some research evidence that stenosis in these arteries are the root of that issue, so many cardiologists will be interested in their size if surgery is in the cards.
The third area that many doctors keep an eye on are the renal arteries. These feed blood to the kidneys so that liquid waste can be filtered out. The kidney relies on high blood pressure to function properly and stenosis here can cause many issues in a person's ability to control waste levels in their bloodstream. This occurs in 45% of people with WS.
Image from University of Virgina
Other heart issues
80% of individuals with WS have some sort of heart abnormality. Although high blood pressure and narrow vessels are the most common issues among those with WS, other issues can pop up. The other common condition, which occurs in 10% of those with WS, are ventricular septal defects or VSD's. The heart is made up of four chambers, two atriums and two ventricles. The ventricles or lower chambers are seperated by membranes and a thick muscle wall. This functions to provide push when the ventricle contracts and to separate blood on the right side that is filled with carbon dioxide from the blood on the left that has oxygen.
VSD's are holes that are in that muscle wall. They allow blood to mix and essentially decrease the amount of oxygen that gets to your tissues. If the hole is very large it would need to be patched in open heart surgery. If the hole is small, it will often close on its own as the person grows. The muscle in the heart increases in size as the person grows and will eventually grow into that space and close the hole. Therefore, VSD's are usually only an issue during infancy.
Monitoring the heart
It is important for all individuals with WS to have their heart and vessels regularly monitored by a cardiologist. Cardiologists will take blood pressure readings and look at the heart and vessels using an electrocardiogram (echo). The echo is essentially an ultrasound machine that a technician will use to take photographs of the heart and vessels, take measurements of their sizes and use a doppler setting to monitor blood flow.
When things go wrong
A parent or caregiver for an individual with WS should really be educated to look for signs of congestive heart failure. If the stenosis becomes so narrow that blood is not properly moving through the body, there will be definite signs. The limbs, feet and hands will be cold due to poor circulation. Fluid will build up in the body since the blood cannot move as freely. The first organs that will become filled with fluid are the lungs. The excess fluid will take up space where air once used so the person will have labored breathing. Their breathing will speed up so the body can get the oxygen that it needs. The muscles in the chest will also work harder to try and move more air into the lungs. You'll notice the muscle pulling in at the ribs and in the base of the neck. The decreased lung volume coupled with poor circulation will lead to less oxygen in the tissues. Oxygen makes your blood red when it touches or binds with our red blood cells. When the blood has no oxygen it turns blue (that's why your veins are blue). Since less oxygen would reach the tissue in the body, areas of the skin will turn blue or gray (called cyanosis) . The first place this will be evident are in the mouth and gums. The lack of oxygen will also mean the person cannot create usable energy so they will become very tired easily; even eating will become taxing.
If you see any of these symptoms, it could mean that the heart is failing to move blood through the body and you should go to the hospital right away. They will be able to determine what in the system is going wrong and how to fix it. Often, they will use the echo. In congestive heart failure, the heart will often have larger muscle mass. This is the body's way of overcompensating for the poor circulation. The muscle will build up so it can give a stronger push and create a higher blood pressure to move the blood through.
How it's fixed
If you get to the point where congestive heart failure is occurring, surgery will probably come up during discussion. The cardiologist will monitor the size of the stenosis and any other heart conditions that are also present. If the space is not considered too narrow, they will most likely continue monitoring and prescribe a medication called a diuretic. Diuretics signal the kidneys to absorb more water from the body and pass it out through the urine. This will decrease the amount of fluids in the body and relieve the fluid build up that causes issues in the lungs. If the narrowing is not severe and the person's pressure and fluid balance can be controlled using a diuretic, surgery may not be necessary.
In some people, the stenosis can be so severe that the vessel needs to be surgically enlarged to allow more blood to move through. Essentially, the surgery would "add lanes to the highway". Surgeons can accomplish this without doing open heart surgery. If they are enlarging stenosis in the aorta, they will often open up the chest cavity by making an incision through the patient's back in between the ribs. This of course depends on where the narrowing occurs. Then, they cut an area of the vessel and sew in a patch that increases the size of the opening.
The severity of stenosis in individuals with Williams syndrome is highly variable. Some people never have problems with it throughout their lives whereas others need surgery soon after being born. It depends on the individual. It is important to understand that stenosis is a fickle issue that can change throughout the person's life. It's most commonly a larger issue in infants and toddlers but it doesn't "go away" in adulthood. This is why it's important to see a cardiologist regularly.
Sources
Cardiovascular Disease in Williams Syndrome by Dr. Thomas Collins; 2015
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