Genetic mutations: People have 23 pairs of chromosomes, for a total of 46 chromosomes. People inherit one set (23 chromosomes) from each of their parents. Williams syndrome occurs when a person is missing a specific part of chromosome 7. The deleted region of chromosome 7 that is associated with Williams syndrome includes more than 20 different genes. Scientists believe that symptoms of Williams syndrome occur because a person is missing several of these genes, particularly CLIP2, ELN, GTF2I, GTF2IRD1, LIMK1, and NCF1 genes. The severity and extent of genetic deletions vary among patients.
The ELN gene contains genetic information for making elastin, which is an important component of connective tissue. Deletions of the ELN gene may cause connective tissue abnormalities (such as flexible joints) and heart disease in people with Williams syndrome.
Research also suggests that the deletion of other genes, including the LIMK1, GTF2I, and GTF2IRD1 genes, may lead to poor visual and spatial abilities. The distinctive facial characteristics associated with Williams syndrome may also be a result of the absence of the GRF2IRD1 gene.
Patients with Williams syndrome who lack the NCF1 gene tend to have lower risks of developing high blood pressure (hypertension). Deletions of the NCF1 gene in Williams syndrome may also affect behavior, personality, and intellectual ability.
Researchers are currently performing studies to determine exactly how other genetic deletions cause symptoms of Williams syndrome.
Random occurrence: Nearly all cases of Williams syndrome are not inherited. Instead, they occur when a genetic mutation randomly occurs during the development of the egg, sperm, or embryo.
Inheritance: In very rare cases, Williams syndrome may be passed down as an autosomal dominant disorder. This means that a person who has just one mutated chromosome 7 has the disorder. If one parent has Williams syndrome, there is a 50% chance that his/her child will have Williams syndrome. If both parents have Williams syndrome, there is a 75% chance that the child will inherit the condition.
General: Williams syndrome is generally diagnosed based on the patient's clinical signs and symptoms and analysis of his/her chromosomes. Children are generally diagnosed shortly after birth because most signs and symptoms (especially the characteristic facial features) are apparent at birth.
FISH test: A FISH (fluorescence in situ hybridization) test is a specialized chromosome analysis that uses fluorescent probes that specifically label the elastin (ELN) gene, which is deleted in 98-99% of patients with Williams syndrome. If two copies of the ELN gene are present in the patient's cells (one on each copy of chromosome 7), he or she probably does not have Williams syndrome. If the person only has one copy, the diagnosis of Williams syndrome is confirmed. Results are usually available within 2-4 weeks.
signs and symptoms
General: Williams syndrome generally causes mild to moderate intellectual or learning disabilities, distinctive facial features, and unique personality characteristics that include overfriendliness, anxiety, and high levels of empathy.
Abdominal pain: Long-lasting (chronic) abdominal pain is common in adolescents and adults with Williams syndrome.
Behavioral problems: Infants with Williams syndrome are often irritable and cry excessively for no obvious reason. More than 50% of people with Williams syndrome have attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD). About 50% have phobias or extreme fears of things that pose little or no danger. For instance, some patients may be extremely afraid of loud noises. Most people with Williams syndrome have anxiety and worry excessively.
Connective tissue abnormalities: Connective tissue, such as tendons, ligaments, and cartilage, provide the framework of the body. Some people with Williams syndrome have connective tissue abnormalities, such as flexible joints, stiff joints, or soft, loose skin. Patients may also have decreased motor coordination and balance, as well as reduced muscle tone.
Feeding difficulties: Infants may also have feeding problems that are often linked to reduced muscle tone, severe gag reflex, and difficulty sucking or swallowing. These difficulties tend to improve as the infant grows.
Hypercalcemia: Infants with Williams syndrome often have a high level of calcium in the blood, a condition called hypercalcemia. This condition may lead to kidney stones called calcium stones.
Intellectual disabilities: People with Williams syndrome typically have mild to moderate forms of intellectual disabilities. Intellectual disabilities (formerly called mental retardation) cause significantly impaired cognitive functioning beginning at birth or early infancy. Intellectual disabilities limit the individual's ability to perform normal daily activities.
People with Williams syndrome often share many of the same cognitive strengths and weaknesses. For example, patients often have strong short-term memories and language skills. They often use expressive vocabulary and are able to learn new and unusual words quickly. Many are able to follow unconventional sentence structures, such as those that use the passive voice. Patients often have poor visual and spatial abilities, which often makes it difficult for them to draw, write, or copy patterns.
Learning disabilities: People with Williams syndrome may also have learning disabilities. Learning disabilities are disorders that occur when patients have difficulty interpreting or processing what they see or hear. It does not mean they are unintelligent. It means that they learn and process new information differently than the average person. Patients may have difficulties with spoken and written language, self-control, coordination, and/or attention. As a result, patients may have a hard time with schoolwork or performing tasks at work.
Physical characteristics and facial features: Young children with Williams syndrome typically have distinctive facial features, including a broad forehead, a short nose with a broad tip, full cheeks, puffiness around the eyes, a wide mouth with full lips, a small chin, and teeth that are spaced far apart. In older children and adults, the face often appears longer than normal. The disorder is sometimes called "elfin-facies" because these distinct facial characteristics may appear to be elf-like. People with the disorder may also have a longer than normal neck, short stature, sloping shoulders, limited mobility of the joints, and a curved spine (called scoliosis). Some people with Williams syndrome may have star-like patterns in the iris of their eyes.
Unique personality characteristics: People with Williams syndrome are often overfriendly and have high levels of empathy, which is the ability to understand another person's feelings. Also, researchers have identified a link between children with Williams syndrome and an affinity for music. This means that patients usually enjoy participating in musical activities. Evidence shows that children are often able to stay focused longer on activities that involve music than non-musical activities. Patients with Williams syndrome appear to have a slightly higher rate of musicality, and some may even be musically gifted. However, many people with the disorder are not.
Diabetes: Most people with Williams syndrome have diabetes or pre-diabetes by age 30. Pre-diabetes occurs when a person's blood sugar is higher than normal, but not quite high enough to be diagnosed as diabetes.
Hearing loss: Most people with Williams syndrome experience mild to moderate hearing loss that is caused by a disturbed function of the auditory nerve. For some, hearing loss may begin in late childhood.
Heart failure: People with Williams syndrome have an increased risk of experiencing heart failure, a degenerative condition that occurs when the heart is unable to beat efficiently and to pump enough blood to meet the body's needs. People with Williams syndrome have an increased risk of developing heart failure because they often have narrowed blood vessels. Heart failure is a long-term condition that generally worsens over time.
High blood pressure: People with Williams syndrome have an increased risk of developing high blood pressure, also known as hypertension. This is because the blood vessels may be narrower than normal. The risk of hypertension tends to be lower in patients who lack the NCF1 gene.
Supravalvar aortic stenosis (SVAS): A type of heart disease called supravalvar aortic stenosis (SVAS) is very common among patients with Williams syndrome. This condition causes the aorta, the large blood vessel that carries blood from the heart to the rest of the body, to narrow over time. Without treatment, SVAS may cause chest pain, shortness of breath, and heart failure.
Nearly all cases of Williams syndrome occur randomly and are not inherited. Therefore, the condition usually occurs when there is no family history of the disorder.
In rare cases, Williams syndrome may be inherited or passed down among family members. In such cases, the disorder is inherited as an autosomal dominant condition. This means that only one copy of the mutated gene is needed for a person to have the disorder. In other words, if one parent has Williams syndrome, there is a 50% chance that the child will inherit the disorder. If both parents have Williams syndrome, there is a 75% chance that the child will inherit the condition.