Williams Syndrome: The “Happy” Syndrome
“Williams Syndrome occurs with a frequency of 1 in every 10,000-20,000 individuals.”
Brief Summary of Disease
When you meet someone new, you may expect them to give you a handshake or a few warm words, but imagine if you were greeted with a big hug instead. Some people may be delightfully surprised, while others will feel uncomfortable and annoyed. This extreme friendliness is what those with Williams Syndrome experience. Williams Syndrome is a genetic disorder, characterized by a variety of physiological and cognitive symptoms that can produce unique social challenges for afflicted individuals. Those with Williams Syndrome face not only physiological challenges, but they also experience the unique social challenge of being “too friendly” and oftentimes too trusting.1 Williams Syndrome occurs with a frequency of 1 in every 10,000-20,000 individuals.2 Although it is rare, it may be more common than originally thought due to the lack of diagnosis. The condition is characterized by a deletion of a region in chromosome number 7,2 which causes patients’ symptoms to vary greatly in both range and severity. It equally affects females and males and may impact all races.2
“The disease is caused by a deletion of 26-28 genes within chromosome 7, including CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1.”
Etiology & Pathology
Although most cases of Williams Syndrome are spontaneous, some individuals inherit it from family members. The disease is caused by a deletion of 26-28 genes within chromosome 7, including CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1.
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Given that these genes control many specific functions, their absence is responsible for many of the symptoms patients experience. For example, the CLIP2 gene plays a role in the normal structure and function of nerve cells in the brain as it regulates components of the cell and its environment.
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It is hypothesized that the deletion of this gene results in the unique social traits and intellectual deficiency in individuals with Williams Syndrome. The ELN gene is important in connective tissue and its deletion may cause cardiovascular problems like supravalvular aortic stenosis, which is the narrowing of a major blood vessel of the heart.
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The LIMK1 gene affects axon growth and brain development, which may cause impaired visuospatial constructive cognition, the ability to identify the individual parts of a full object or picture.
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As the disease is present since birth, those with it are likely to experience many of the same symptoms throughout their lives.
“Although individuals with Williams Syndrome have intellectual and developmental disabilities such as ADHD, a very large range of vocabulary and language is usually present, with exceptional long-term memory and an outgoing personality.”
Symptoms
The signs and symptoms of someone with Williams Syndrome varies greatly, contributing to its lack of diagnosis and subsequent underestimated frequency. Symptoms include unique facial structure, cardiovascular issues and intellectual deficits, among others. The affected patient is often described as “elfin-like” because of their smaller head size (microcephaly), full cheeks, broad forehead, low nose bridge, and puffy eyes.
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The majority of patients -- around 75% -- have congenital heart defects, which are irregularities in the structure of the heart that are present from birth. Children with the condition may have low birth weight, shorter stature, and elevated calcium levels that resolve after 1 year. A heightened sensitivity to loud sounds (hyperacusis) and delayed motor skills may also be present in these individuals. Adults with Williams Syndrome are more likely to develop joint problems and skeletal abnormalities. .
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Perhaps the most unique trait of Williams Syndrome is the characteristic personalities of those affected. Although individuals with Williams Syndrome have intellectual and developmental disabilities such as ADHD, a very large range of vocabulary and language is usually present, with exceptional long-term memory and an outgoing personality.
2
Children with Williams Syndrome have a higher degree of empathy and sociability than other children, possibly due to the deletion of the CLIP2 gene.
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Overall, Williams Syndrome presents varying symptoms that are ongoing throughout the life of those who are affected, but negative effects may be minimized through treatment and support.
Diagnosis
Williams Syndrome is first suspected in children due to its physiological and behavioural effects, as well as its characteristic “elfin-like” physical appearance. It can be confirmed with either a microarray analysis, which measures DNA expression levels, or a FISH blood test.1 The microarray analysis can determine the length of deletion in chromosome 7 and the FISH test looks for the absence of the ELN gene, which is a marker for Williams Syndrome.
The disease is often under-diagnosed or patients are diagnosed at a later age because its symptoms can present clinically similar to a variety of other conditions.2 For example, an affected child may have ADHD, struggle in school, and have trouble making friends. These behavioural effects can be attributed to many other developmental and intellectual disabilities. The lack of diagnosis prevents patients and their families from getting the support that they need. This is important, as early therapeutic interventions can drastically improve the quality of life for patients and allow them to reach their full potential.
“Although the average life expectancy is lower than the general population’s, with proper treatment and support, patients can live very long lives. ”
Prognosis
There is currently no cure for Williams Syndrome, but that does not mean that patients cannot live a fulfilling life. Although the average life expectancy is lower than the general population’s, with proper treatment and support, patients can live very long lives. Because the majority of those affected have cardiovascular problems, a specialist is essential in diagnosing the specific diseases, as well as providing treatment with the appropriate medication. In severe cases, sometimes surgery is necessary. A change in diet may be required to restrict calcium intake and ensure that calcium levels do not reach dangerously high levels. The use of speech therapy, physical therapy, and specialized education can also allow patients to thrive, especially if such programs are initiated at a young age. 1
Current Research
Much of the current research surrounding Williams Syndrome revolves around understanding the disease itself, rather than trying to “cure” it. Although specific gene deletions are identified that contribute to the overall symptomology of Williams Syndrome, little is known about the functions and mechanisms of each gene. The majority of research is focused on the cardiovascular effects of the disease, as well as its cognitive and behavioural aspects. It has been found that those with Williams Syndrome have brain abnormalities, specifically damage to myelin sheaths.8 Myelin sheaths help to transmit brain signals and its deficit is known to cause neurological and psychiatric disorders. Some clinical studies have also shown that children with Williams syndrome have an above average proficiency in language, which often contributes to the lack of diagnosis and educational support.9
There are specific research projects that focus on Williams Sydrome and its physiological and social effects. One such initiative is The Chromosome 7 project . It is part of the Human Genome project which is being conducted at the Hospital for Sick Children in Toronto. This research group focuses on the genes within chromosome 7, and how their alterations contribute to many different genomic conditions. Some other conditions associated with chromosome 7 include muscular dystrophy and cystic fibrosis.
Anna Xia
Relevant Resources
The Canadian Association for Williams Syndrome
This is a Canadian organization and is one of the main resources for families that have been affected by Williams Syndrome. They are a parent-volunteer run organization that provides education on the condition, as well as many other supportive services. They spread awareness, raise funds, support research, and connect families who have been affected by Williams Syndrome.
The Williams Syndrome Association (US) and The Williams Syndrome Foundation (UK) are other similar organizations that provide support for those affected by the condition.
Works Cited
1. Morris CA. Introduction: Williams syndrome. InAmerican Journal of Medical Genetics Part C: Seminars in Medical Genetics 2010 May 15 (Vol. 154, No. 2, pp. 203-208). Hoboken: Wiley Subscription Services, Inc., A Wiley Company. doi:10.1002/ajmg.c.30266
2. Williams Syndrome. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/williams-syndrome. Accessed October 21, 2020.
3. Williams syndrome: MedlinePlus Genetics. MedlinePlus 2020. https://medlineplus.gov/genetics/condition/williams-syndrome. Accessed October 21, 2020.
4. Hoogenraad CC, Akhmanova A, Galjart N, De Zeeuw CI. LIMK1 and CLIP‐115: linking cytoskeletal defects to Williams syndrome. Bioessays. 2004 Feb;26(2):141-50. doi:10.1002/bies.10402
5.Sugiyama K, Horigome H, Lin L, Murakami T, Shiono J, Yamashiro Y, Matsuura H, Yoda H, Yanagisawa H. Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis. Molecular Genetics & Genomic Medicine. 2019 Nov;7(11):e986. doi:10.1002/mgg3.986
6. Frangiskakis JM, Ewart AK, Morris CA, Mervis CB, Bertrand J, Robinson BF, Klein BP, Ensing GJ, Everett LA, Green ED, Pröschel C. LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell. 1996 Jul 12;86(1):59-69. doi:10.1016/s0092-8674(00)80077-x
7. Kaplan P, Wang PP, Francke U. Williams (Williams Beuren) syndrome: a distinct neurobehavioral disorder. Journal of child neurology. 2001 Mar;16(3):177-90. doi:10.1177/088307380101600305
Nir A, Barak B. White matter alterations in Williams syndrome related to behavioral and motor impairments. Glia. 2020 Jun 26. doi:10.1002/glia.23868
8. Royston R, Waite J, Howlin P. Williams syndrome: Recent advances in our understanding of cognitive, social and psychological functioning. Current Opinion in Psychiatry. 2019 Mar 1;32(2):60-6. doi:10.1097/YCO.0000000000000477
Cite This Article:
Xia A., Carmona A., Mughal R. Williams Syndrome: The “Happy” Syndrome.Illustrated by C. Qian. Rare Disease Review. January 2021.
DOI: 10.13140/RG.2.2.26010.26568
