Williams syndrome - Rare Rheumatology News

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Disease Profile

Williams syndrome

Unknown

US Estimated

Europe Estimated

Age of onset

Neonatal

ICD-10

Q93.8

Inheritance

Most cases of Williams syndrome are not inherited. The condition typically occurs due to random events during the formation egg or sperm cells in a parent. Therefore, it most often occurs in people with no family history of Williams syndrome.

In a small portion of cases, people with Williams syndrome inherit the chromosome deletion from a parent with the condition.^[1] In these cases, it is inherited in an autosomal dominant manner. This is because having only one changed copy of chromosome 7 in each cell is enough to cause signs and symptoms.

Regardless of whether Williams syndrome occurs randomly or is inherited from a parent, each child of a person with Williams syndrome has a 50% chance of inheriting the condition.^[4]

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Williams-Beuren syndrome; WBS; WMS;

Summary

Williams syndrome is a genetic condition that affects many parts of the body. Signs and symptoms include mild to moderate intellectual disability; unique personality traits; distinctive facial features; and heart and blood vessel problems.^[1] Williams syndrome is caused by a person missing more than 25 genes from a specific area of chromosome 7 (a "deletion").^[1]^[2] The loss of these genes contributes to the characteristic features.^[1] Although Williams syndrome is an autosomal dominant condition, most cases are not inherited and occur sporadically in people with no family history of Williams syndrome. Treatments are based on each person's signs and symptoms, as there is no cure at this time.^[1]^[3]

Symptoms

The signs and symptoms of Williams syndrome can vary, but generally include:^[1]^[3]

mild to moderate intellectual disability;
a distinctive facial appearance;
and a unique personality that combines over-friendliness and high levels of empathy with anxiety.

People with Williams syndrome typically have difficulty with tasks such as drawing and assembling puzzles. They tend to do well on tasks that involve spoken language, music, and learning by repetition.^[1]

Facial features common in young children with Williams syndrome include a broad forehead; a short nose with a broad tip; full cheeks; and a wide mouth with full lips. In older children and adults, the face appears longer and more gaunt. Dental problems are common and may include small, widely spaced teeth and teeth that are crooked or missing.^[1]

People with Williams syndrome often have outgoing, engaging personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common.^[1]

The most significant medical problem associated with Williams syndrome is a form of heart disease called supravalvular aortic stenosis (SVAS). SVAS is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). If this condition is not treated, it can lead to shortness of breath, chest pain, and heart failure. The presence of other heart and blood vessel problems has also been reported.^[1]

Additional signs and symptoms of Williams syndrome may include:^[1]

abnormalities of connective tissue (tissue that supports the body's joints and organs) such as joint problems and soft, loose skin;
increased calcium levels in the blood (hypercalcemia) in infancy;
developmental delays;
problems with coordination;
short stature;
vision and eye problems;
digestive problems; and
urinary problems.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abdominal pain	Pain in stomach Stomach pain [ more ]	0002027
Abnormality of extrapyramidal motor function		0002071
Abnormality of pelvic girdle bone morphology	Abnormal shape of pelvic girdle bone	0002644
Abnormality of the neck		0000464
Anxiety	Excessive, persistent worry and fear	0000739
Blepharophimosis	Narrow opening between the eyelids	0000581
Broad forehead	Increased width of the forehead Wide forehead [ more ]	0000337
Coarse facial features	Coarse facial appearance	0000280
Depressivity	Depression	0000716
Dysgraphia		0010526
Dysmetria	Lack of coordination of movement	0001310
Elfin facies	Elf-like facial appearance Elf-like facial features [ more ]	0004428
Epicanthus	Prominent eye folds Eye folds [ more ]	0000286
Everted lower lip vermilion	Drooping lower lip Outward turned lower lip [ more ]	0000232
Failure to thrive in infancy	Faltering weight in infancy Weight faltering in infancy [ more ]	0001531
Gait imbalance	Imbalanced walk Abnormality of equilibrium Abnormality of balance [ more ]	0002141
High forehead		0000348
High hypermetropia	Severe farsightedness Severe long-sightedness [ more ]	0008499
Hoarse voice	Husky voice Hoarseness [ more ]	0001609
Hyperacusis		0010780
Hypercalcemia	High blood calcium levels Increased calcium in blood [ more ]	0003072
Hyperreflexia	Increased reflexes	0001347
Intellectual disability	Mental deficiency Mental retardation, nonspecific Mental retardation Mental-retardation [ more ]	0001249
Long philtrum		0000343
Low-set, posteriorly rotated ears		0000368
Macroglossia	Abnormally large tongue Increased size of tongue Large tongue [ more ]	0000158
Macrotia	Large ears	0000400
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Narrow face	Decreased breadth of face Decreased width of face [ more ]	0000275
Open bite	Absence of overlap of upper and lower teeth Open bite between upper and lower teeth [ more ]	0010807
Overfriendliness		0100025
Periorbital edema		0100539
Phonophobia	Fear of loud sounds	0002183
Pointed chin	Pointy chin Small pointed chin Witch's chin [ more ]	0000307
Protruding ear	Prominent ear Prominent ears [ more ]	0000411
Short nose	Decreased length of nose Shortened nose [ more ]	0003196
Short stature	Small stature Decreased body height [ more ]	0004322
Thick lower lip vermilion	Plump lower lip Increased volume of lower lip Prominent lower lip [ more ]	0000179
Tremor		0001337
Wide mouth	Broad mouth Large mouth [ more ]	0000154
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431
30%-79% of people have these symptoms
Abnormal fingernail morphology	Abnormal fingernails Abnormality of the fingernails [ more ]	0001231
Abnormality of dental enamel	Abnormal tooth enamel Enamel abnormalities Enamel abnormality [ more ]	0000682
Arthralgia	Joint pain	0002829
Attention deficit hyperactivity disorder	Attention deficit Attention deficit disorder Attention deficit-hyperactivity disorder Attention deficits Childhood attention deficit/hyperactivity disorder [ more ]	0007018
Autism		0000717
Bladder diverticulum		0000015
Blue irides	Blue eyes	0000635
Broad nasal tip	Broad tip of nose Broad, upturned nose Increased breadth of nasal tip Increased breadth of tip of nose Increased width of nasal tip Increased width of Cause Williams syndrome is caused by a missing piece (deletion) of genetic material from a specific region of chromosome 7. The deleted region includes more than 25 genes.^[1] CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted in people with Williams syndrome. Researchers have found that the loss of the ELN gene is associated with the connective tissue abnormalities and heart disease in many people with this condition. Studies suggest that deletions of CLIP2, GTF2I, GTF2IRD1, LIMK1, and perhaps other genes, may help explain many of the unique behavioral characteristics and cognitive difficulties. Loss of the GTF2IRD1 gene may also contribute to the distinctive facial features often present.^[1] The relationship between some of the other deleted genes and the features of Williams syndrome is not yet known.^[1] Diagnosis The diagnosis of Williams syndrome (WS) is established by genetic testing identifying a specific microdeletion at chromosome 7q11.23 (on the long arm of chromosome 7, at a position designated 11.23).^[4] Because the symptoms and severity of WS vary, no single feature is needed to establish the diagnosis.^[4] WS may first be suspected in individuals with: Cardiovascular (heart) disease (elastin arteriopathy) any artery may be narrowed. Supravalvar aortic stenosis (SVAS) is the most common heart abnormality, occurring in 75% of people with WS. Peripheral pulmonic stenosis is common in infancy.^[4] Distinctive facial features broad forehead, a short nose with a broad tip, full cheeks, and a wide mouth with full lips. In older children and adults, the face appears longer and more gaunt.^[1] Connective tissue abnormalities causing a hoarse voice, inguinal or umbilical hernia, bowel or bladder diverticulum, rectal prolapse, joint limitation or laxity, and soft, lax skin.^[4] Intellectual disability some degree is present in most people with WS. Some have average intelligence.^[4] Strengths in verbal short-term memory and language, and extreme weakness in visuospatial construction.^[4] Unique personality overfriendliness, empathy, generalized anxiety, specific phobias, and attention deficit disorder are commonly present.^[4] Growth abnormalities prenatal growth deficiency, failure to thrive in infancy, poor weight gain and growth in the first four years, and a brief pubertal growth spurt.^[4] Endocrine abnormalities such as hypercalcemia, high calcium urine levels (hypercalciuria), hypothyroidism, and early puberty.^[4] Testing Resources The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional. Treatment Treatment for people with Williams syndrome may be individualized depending on the symptoms and severity in each person. Management may include: Feeding therapy for infants with feeding problems Early intervention programs and special education programs for children with varying degrees of developmental disabilities Behavioral counseling and/or medications for attention deficit disorder and/or anxiety Surgery for certain heart abnormalities Medications or diet modifications for hypercalcemia Orthodontic appliances or other treatments for malocclusion of teeth Gonadotropin-releasing hormone agonist for early puberty^[4] Management Guidelines Management guidelines from the American Academy of Pediatrics: Health Care Supervision for Children With Williams Syndrome Pediatrics, Vol. 107 No. 5 May 2001, pp. 1192-1204. A statement of reaffirmation for this policy was published on September 1, 2005 Organizations Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Organizations Supporting this Disease Canadian Association for Williams Syndrome PO Box 2115 Vancouver, BC, V6B 3T5 Canada Telephone: 604-853-0231 Fax: 604-853-0232 Website: https://caws.sasktelwebhosting.com/ Williams Syndrome Association 570 Kirts Blvd Suite 223 Troy, MI 48084-4156 Toll-free: 800-806-1871 Telephone: 248-244-2229 Fax: 248-244-2230 E-mail: info@williams-syndrome.org Website: https://www.williams-syndrome.org Williams Syndrome Foundation Suite 103 145-147 Boston Road, Ealing London W7 3SA, England Telephone: 01732-365152 E-mail: enquiries@williams-syndrome.org.uk Website: https://www.williams-syndrome.org.uk/ Learn more These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional. Where to Start MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic. Genetics Home Reference (GHR) contains information on Williams syndrome. This website is maintained by the National Library of Medicine. The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic. The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them. In-Depth Information GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions. Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free. The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition. Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge. PubMed is a searchable database of medical literature and lists journal articles that discuss Williams syndrome. Click on the link to view a sample search on this topic. References Williams syndrome. Genetics Home Reference (GHR). December 2014; https://ghr.nlm.nih.gov/condition/williams-syndrome. Williams syndrome. MedlinePlus. 2017; https://www.nlm.nih.gov/medlineplus/ency/article/001116.htm. Williams Syndrome Information Page. National Institute of Neurological Disorders and Stroke (NINDS). May 22, 2017; https://www.ninds.nih.gov/Disorders/All-Disorders/Williams-Syndrome-Information-Page. Morris CA. Williams Syndrome. GeneReviews. March 23, 2017; https://www.ncbi.nlm.nih.gov/books/NBK1249/. Rare Rheumatology News Advertisement Features Rare Disease Profiles 5 Facts Rare IQ Rare Mystery Spotlight On News Contact Us Advertising and Sponsorship About The Rare Medical Network Our mission is to inform the healthcare community about the diagnosis and management of rare diseases. Help us by sharing this important information with your peers. Rare Medical News websites sources information from: Orpha Net, The Genetic and Rare Diseases Information Center (GARD), PubMed and ClinicalTrials.gov. Rare Rheumatology News is strictly a news and information website about rare diseases. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. © 2024 Rare Rheumatology News. All Rights Reserved. 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Rare Rheumatology News

Rare Rheumatology News

Neonatal

Q93.8

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Management Guidelines

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.