Related Terms

• ADHD, attention deficit hyperactivity disorder, autosomal dominant disorder, autosomal dominant trait, Beuren syndrome, chromosomal deletion, chromosome 7, CLIP2 gene, early hypercalcemia syndrome, elastin, elfin facies syndrome, elfin facies with hypercalcemia, ELN gene, FISH, fluorescent in situ hybridization, general transcription factor II I gene, GTF2I gene, GTF2I repeat domain containing 1 gene, GTF2IRD1 gene, hypercalcemia, hypertension, infantile hypercalcemia, intellectual disabilities, learning disabilities, LIM domain kinase 1 gene, LIMK1 gene, NCF1 gene, neutrophil cytosolic factor 1 gene, supravalvar aortic stenosis, SVAS, WBS, Williams-Beuren syndrome, William's syndrome, WMS.

Background

• Williams syndrome, also called Williams-Beuren syndrome, is a genetic disorder that typically causes mild to moderate intellectual or learning disabilities, distinctive facial features, and unique personality characteristics that include overfriendliness, anxiety, and high levels of empathy. Infants with Williams syndrome often have high levels of calcium in their blood (called hypercalcemia).

• The most significant medical problem associated with Williams syndrome is a form of heart disease called supravalvar aortic stenosis (SVAS), in which the main blood vessel of the heart (the aorta) is too narrow.

• Researchers estimate that one out of 7,500 to 20,000 people is born with Williams syndrome worldwide.

• The prognosis for patients with Williams syndrome varies depending on the severity of the person's intellectual disabilities and heart problems. With early diagnosis and prompt therapy, some patients are able to live independently once they become adults, while others may need lifelong support. There are many ways for patients to cope with their disabilities. Special education and occupational therapy has been shown to improve patients' work and school performance.

Risk Factors

• 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.

Causes

• 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.

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.

Diagnosis

• 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.

Complications

• 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.

Treatment

• General: With early diagnosis and prompt therapy, some patients are able to live independently once they become adults, while others may need lifelong support. There are many ways for patients to cope with their disabilities. Special education and occupational therapy has been shown to improve patients' work and school performance.

• Patients should regularly visit their doctor and cardiologist (heart doctor) to monitor their condition and help prevent complications.

• Childhoodintervention programs: Patients with Williams syndrome typically experience physical and intellectual developmental delays. For instance, it may take a child with Williams syndrome longer to crawl or walk than a healthy child. Therefore, caregivers should ask the doctors of Williams syndrome patients about early intervention programs. These specialized programs expose disabled children to age-appropriate sensory, motor, and cognitive activities. These programs typically involve special educators and therapists who help babies and young children develop their language, social, and motor skills. Proper therapy and education may also help children with activities of daily living.

• Education: Patients with Williams syndrome who suffer from intellectual or learning disabilities must have access to education that is tailored to their specific strengths and weaknesses. According to the Individuals with Disabilities Education Act, all children with disabilities must receive free and appropriate education. According to the law, members of the patient's school should consult with the patient's parents or caregivers to design and write an individualized education plan. The school faculty should document the child's progress in order to ensure that the child's needs are being met.

• Educational programs vary among patients. In general, most experts believe that children with disabilities should be educated alongside their non-disabled peers. The idea is that non-disabled students will help the patient learn appropriate behavioral, social, and language skills. Therefore, some Williams syndrome patients are educated in mainstream classrooms. Other patients attend public schools but take special education classes. Others attend specialized schools that are designed to teach children with disabilities.

• Behavioral therapy: Behavioral therapy may also be beneficial. Several different types of behavioral therapy are available to help Williams syndrome patients improve their communication and social skills, as well as their learning abilities and adaptive behaviors. Therapy may also help reduce negative behaviors, such as aggression, temper tantrums, and hyperactivity. For instance, dialectical behavior therapy may be used to teach behavioral skills to help a person tolerate stress, regulate emotions, and improve relationships with others. It may also help patients learn how to react and behave when they feel anxious. Evidence suggests that behavioral therapy is most effective if it is started early in life.

• Speech-language therapy: Some patients with Williams syndrome may benefit from speech-language therapy because individuals often develop communication skills slower than normal. Although it may take children with Williams syndrome longer to learn communications skills, they often develop strong speaking abilities when they are older. In fact, they often use expressive vocabulary and are able to learn new and unusual words quickly.

• During speech-language therapy, a qualified speech-language professional (SLP) works with the patient on a one-to-one basis, in a small group, or in a classroom to help the patient improve speech, language, and communication skills. Programs are tailored to the patient's individual needs.

• Speech pathologists use a variety of exercises to improve the patient's communication skills. Exercises typically start off simple and become more complex as therapy continues. For instance, the therapist may ask the patient to name objects, tell stories, or explain the purpose of an object.

• On average, patients receive five or more hours of therapy per week for three months to several years. Doctors typically recommend that treatment is started early to ensure the best possible prognosis for the child.

• Physical therapy: Physical therapy may help some patients with Williams syndrome improve their balance, coordination, muscle strength, and joint mobility. A variety of techniques, including exercises, stretches, traction, electrical stimulation, and massage, are used during physical therapy sessions.

• Surgery: Surgery is typically performed to treat supravalvar aortic stenosis (SVAS) in patients with Williams syndrome. If the artery is an hourglass shape, the narrowed part of the artery may be cut out and covered with a patch. If the narrowing is spread throughout the aorta, the ascending aorta and aortic arch may be reconstructed with tube graft replacement. About five percent of patients with hourglass shaped aortas die during surgery, compared to fewer than 12% of patients with diffuse narrowing.

Integrative Therapies

• Note: Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Williams syndrome. However, some therapies have been studied as treatments for attention deficit hyperactivity disorder (ADHD), a condition that affects more than 50% of patients with Williams syndrome. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies or preventive measures.

• Good scientific evidence:

• Zinc: Clinical study has shown a correlation between low serum free fatty acids and zinc serum levels in children with attention deficit hyperactivity disorder. It has also been found that zinc supplements reduced hyperactive, impulsive, and impaired socialization symptoms, but did not reduce attention deficiency symptoms. Zinc supplementation may be a more effective treatment for older children with higher body mass index (BMI) scores.

• Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

• Unclear or conflicting scientific evidence:

• Flaxseed and flaxseed oil (Linum usitatissimum): Preliminary evidence supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to attention deficit hyperactivity disorder (ADHD). Based on preliminary clinical evidence, alpha linolenic acid-rich nutritional supplementation in the form of flax oil may improve symptoms of ADHD. More research is needed to confirm these results.

• Flaxseed has been well-tolerated in studies for up to four months. Avoid if allergic to flaxseed, flaxseed oil, or other plants of the Linaceae family. Avoid with prostate cancer, breast cancer, uterine cancer, or endometriosis. Avoid the ingestion of immature flaxseed pods. Avoid large amounts of flaxseed by mouth and mix with plenty of water or liquid. Avoid flaxseed (not flaxseed oil) with a history of esophageal stricture, ileus, gastrointestinal stricture, or bowel obstruction. Avoid with a history of acute or chronic diarrhea, irritable bowel syndrome, diverticulitis, or inflammatory bowel disease. Avoid topical flaxseed in open wounds or abraded skin surfaces. Caution is advised with a history of bleeding disorders or with use of drugs that cause bleeding risk (like anticoagulants and non-steroidal anti-inflammatories such as aspirin, warfarin, Advil®), high triglyceride levels, diabetes, mania, seizures, or asthma. Avoid if pregnant or breastfeeding.

• Gamma linolenic acid (GLA): Clinical trials investigating the effect of GLA on symptoms associated with attention-deficit disorder are limited. Evidence of effectiveness of treatment with GLA is currently lacking in the available literature. Additional study is needed in this area. Use cautiously with drugs that increase the risk of bleeding, like anticoagulants and anti-platelet drugs. Avoid if pregnant or breastfeeding.

• Glyconutrients: Glyconutrients are supplements that contain monosaccharides (sugar-type molecules), which are required for the synthesis of glycoproteins (substances which help form hormones and immune system components). The effect of a glyconutritional product has been investigated in children with ADHD. A decrease in the number and severity of symptoms was noted. Additional study is needed in this area.

• Allergy to glyconutrients has not currently been reported in the available literature. However, since glyconutrients are often found in foods or plants, side effects may occur when eating any herb or supplement with glyconutrients. Use cautiously with iron supplements, history of copper deficiency, or history of vitamin B12 deficiency. Glyconutrients are considered important for pregnant and breastfeeding women. However, human clinical trials have not investigated the therapeutic use of these nutrients.

• Iron: Based on preliminary data, taking iron orally might improve the symptoms of attention deficit-hyperactivity disorder (ADHD). A recent study found a three year-old child with ADHD and low iron levels improved significantly on ADHD testing scores after an eight-month treatment with ferrous sulfate, 80 milligrams daily. Caution should be used when taking iron supplements as drug interactions are possible.

• Avoid if known allergy/hypersensitivity to products containing iron. Avoid excessive intake. Avoid iron supplements with blood disorders that require frequent blood transfusions. Use iron supplements cautiously with a history of kidney disease, intestinal disease, peptic ulcer disease, enteritis, colitis, pancreatitis, hepatitis, or alcoholism. Avoid in those who plan to become pregnant or are over age 55 and have a family history of heart disease. Pregnant or breastfeeding women should consult a healthcare professional before beginning iron supplementation.

• L-carnitine: Preliminary clinical study has reported positive effects of using L-carnitine (also called acetyl-L-carnitine) supplements in children (boys) with ADHD. Acetyl-L-carnitine is an antioxidant and may help blood flow as well as neurological function.

• Avoid with known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, and diabetes. Use cautiously in low birth weight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.

• Massage: Preliminary research suggests that massage therapy may improve mood and behavior in children with ADHD. Avoid with bleeding disorders, low platelet counts, or if on blood-thinning medications (such as heparin or warfarin/Coumadin®). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously with a history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.

• Melatonin: There is some research on the use of melatonin in children with ADHD both in the treatment of ADHD and insomnia. Melatonin is not used for extended periods of time. Interactions with drugs may occur. There are rare reports of allergic skin reactions after taking melatonin by mouth. Avoid with bleeding disorders or if taking blood thinners. Use cautiously with seizure disorders, major depression, psychotic disorders, diabetes, low blood sugar levels, glaucoma, high cholesterol, atherosclerosis, or if at risk of heart disease. Use cautiously if driving or operating heavy machinery.

• Music therapy: Music has been found to be relaxing and may cause reduced heart rate, reduced blood pressure, reduced tension, and other beneficial effects. Evidence that music therapy may lead to the relaxation response has been found in healthy individuals and individuals with health problems. More study is needed in the area of ADHD.

• Pycnogenol®: Pycnogenol® is a potent antioxidant that may be effective in decreasing neurological imbalances. Preliminary research comparing Pycnogenol® with placebo in adults with ADHD reported improved concentration with both agents. In more recent studies in children, improvements in attention and various rating scales were noted with Pycnogenol® supplementation.

• Pycnogenol is reported to be safe in recommended dosages. If pregnant or breastfeeding, consult a qualified healthcare provider. Avoid if allergic/hypersensitive to pycnogenol, its components, or members of the Pinaceae family. Use cautiously with diabetes, hypoglycemia, and bleeding disorders. Use cautiously if taking hypolipidemics, medications that may increase the risk of bleeding, hypertensive medications, or immune stimulating or inhibiting drugs.

• SAMe: S-adenosylmethionine, or SAMe, is formed in the body from the essential amino acid methionine and is used in depression and mood disorders. Preliminary evidence from an open trial suggests that SAMe may be of benefit for adults with ADHD. Additional research is needed in this area.

• Caution should be used when taking SAMe supplements as drug interactions are possible. Avoid if allergic or hypersensitive to SAMe. Use cautiously with diabetes and anxiety disorders. Avoid with bipolar disorder. Avoid during the first trimester of pregnancy or if breastfeeding; use cautiously in women in the third trimester of pregnancy.

• Vitamin B6 (Pyridoxine): Some research suggests that pyridoxine supplementation alone or in combination with high doses of other B vitamins may help patients with ADHD. Vitamin B6 may also be found in a multivitamin or a B-complex vitamin supplement.

• Avoid vitamin B6 products if sensitive or allergic to any ingredients in the product. Some individuals seem to be particularly sensitive to vitamin B6 and may have problems even at lower doses. Avoid excessive dosing. Vitamin B6 is likely safe when used orally in doses not exceeding the Recommended Dietary Allowance (RDA). Use cautiously if pregnant or breastfeeding.

• Yoga: There is limited clinical study of yoga for the treatment of ADHD. Further research is needed before a recommendation can be made.

• Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid certain inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Certain yoga breathing techniques should be avoided in people with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction (the popular Lamaze techniques are based on yogic breathing). However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

• Traditional or theoretical uses lacking sufficient evidence:

• Biofeedback: Ordinarily, this stress-reduction technique is used to help people learn to control certain body responses, such as heart rate and muscle tension. It has also been used with the intent of teaching adults and children with ADHD to change their brain wave patterns to more normal ones.

• Although biofeedback is generally considered safe, consult with a qualified healthcare professional before making decisions about new therapies and/or related health conditions. Biofeedback may interfere with the use of some medications, such as insulin. Behavioral modification therapies should not delay the time to diagnosis or treatment with more proven therapies and should not be used as the sole approach to illnesses.

• Omega-3 fatty acids: Essential fatty acids have many roles in the body, including functioning in proper nerve and brain activity. Preliminary evidence supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to ADHD. More research is needed in this area.

• Avoid if allergic or hypersensitive to fish, omega-3 fatty acid products that come from fish, nuts, linolenic acid, or omega-3 fatty acid products that come from nuts. Avoid during active bleeding. Use cautiously with bleeding disorders, diabetes, low blood pressure, or drugs, herbs, or supplements that treat any such conditions. Use cautiously before surgery. The Environmental Protection Agency (EPA) recommends that intake be limited in pregnant/nursing women to a single 6-ounce meal per week, and in young children to less than 2 ounces per week. For farm-raised, imported, or marine fish, the U.S. Food and Drug Administration (FDA) recommends that pregnant/nursing women and young children avoid eating types with higher levels of methylmercury, and less than 12 ounces per week of other fish types. Women who might become pregnant are advised to eat 7 ounces or less per week of fish with higher levels of methylmercury, or up to 14 ounces per week of fish types with about 0.5 parts per million of methylmercury (such as marlin, orange roughy, red snapper, or fresh tuna).

• Fair negative scientific evidence:

• Evening primrose oil (Oenothera biennis L.): Small human studies have shown no benefit from use of evening primrose oil in ADHD. Further research is needed to confirm these findings.

• Psychotherapy: Psychotherapy is an interactive process between a person and a qualified mental health professional. Psychotherapy may not improve parenting, enhance academic achievement, or improve emotional adjustment for children aged 7-9 with ADHD. It is unclear whether psychotherapy would reduce the use of stimulants, such as methylphenidate, in these children. More studies are needed in this area.

Prevention

• There is currently no known method of prevention against Williams syndrome. Nearly all cases of the disorder occur randomly and are not inherited. However, people with Williams syndrome may pass the disorder to their children.

• Early diagnosis and prompt treatment is important to ensure that a person with Williams syndrome maximizes his/her intellectual potential. This is because therapy has been shown to be most effective when started early in life.

• People who are diagnosed with Williams syndrome should regularly visit their doctors and cardiologists (heart doctors) to monitor their conditions and help prevent complications.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Canadian Association for Williams Syndrome. www.caws-can.org.

2. Deutsch SI, Rosse RB, Schwartz BL. Williams syndrome: a genetic deletion disorder presenting clues to the biology of sociability and clinical challenges of hypersociability. CNS Spectr. 2007 Dec;12(12):903-7. View Abstract

3. Gallo FJ, Klein-Tasman BP, Gaffrey MS, et al. Expecting the worst: Observations of reactivity to sound in young children with Williams syndrome. Res Dev Disabil. 2007 Nov 16. View Abstract

4. Lashkari A, Smith AK, Graham JM Jr. Williams-Beuren syndrome: an update and review for the primary physician. Clin Pediatr (Phila). 1999 Apr;38(4):189-208. View Abstract

5. National Institute of Child Health and Human Development (NICHD). www.nichd.nih.gov.

6. National Institutes of Health (NIH). www.nih.gov.

7. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

8. Pober BR, Morris CA. Diagnosis and management of medical problems in adults with Williams-Beuren syndrome. Am J Med Genet C Semin Med Genet. 2007 Aug 15;145(3):280-90. View Abstract

9. Tsai SW, Wu SK, Liou YM, et al. Early development in Williams syndrome. Pediatr Int. 2008 Apr;50(2):221-4. View Abstract

10. Williams Syndrome Association. www.williams-syndrome.org.

11. Williams Syndrome Foundation. www.williams-syndrome.org.uk.