A Mystery of Misinterpretation: Landau on Williams Syndrome

Arts and Sciences Magazine:

"After a decade of research, cognitive scientist Barbara Landau is mapping new territory in Williams syndrome—a rare condition that has long baffled scientists.

Suppose you had a winning personality, you loved music, you could ski, ride a bike, and were about to start college. But when faced with a simple test of matching four painted toy blocks, you fumbled around like a 4-year-old.

How can someone be proficient in so many ways, yet stymied by such a seemingly simple task?

It's a mystery that scientist Barbara Landau—the Dick and Lydia Todd Professor of Cognitive Science at the Zanvyl Krieger School of Arts and Sciences—has spent more than a decade trying to understand."

Tipped by: Stacia

Williams Syndrome eBook Downloads

williams syndrome eBook Downloads

I have not used this site before, but the few I tried seemed to work fine. There are a number of helpful articles here, all in pdf format for easy download.

Williams syndrome associated with complete atrioventricular septal defect

Williams syndrome associated with complete atrioventricular septal defect:

"To our knowledge, this is the first description in the literature of a long follow up period of Williams syndrome associated with complete atrioventricular septal defect. During 10 years’ follow up, the pressure gradient in the ascending aorta did not increase despite the narrowing of the ascending aorta seen on the aortogram."

A Study of Musical Talents and Persons With Williams Syndrome

A Study of Musical Talents and Persons With Williams Syndrome

Click on link above for a full pdf of the study results.

A brief narrative description of the journal article, document, or resource.

This monograph describes the Music & Minds program, which was designed through the collaboration of educational psychology professors specializing in gifted and talented education with faculty members in music, drama, and creative movement. The purpose of the research was to investigate the implications and impact of a strengths- and interests-based program on a special needs group of young adults with Williams syndrome (WS). This exploratory study employed multiple methodologies. Comparative case study and descriptive analysis were used to examine the experiences of the participants, and a mixed methods approach provided input into the effectiveness of using music (a self-reported area of interest) to achieve gains in a demonstrated deficit area (fractions). The Schoolwide Enrichment Model (SEM), a comprehensive, well-researched approach to enrichment, was selected as the conceptual framework for Music & Minds. Instruments used were either developed specifically for the study or adapted from SEM programs to provide group profiles and individual insights into interests and learning preferences. The participants, 8 female and 8 male young adults with WS, exhibited strong affinity for music and sound. There was a wide range of demonstrated musical ability, operationally defined as "the ability to understand and improvise in music, as well as the high level of skills, both potential skill areas and those present that can be developed in music." Findings from the 10-day residential program showed that when academic learning was incorporated into an enriched music-infused curriculum, achievement increased and enthusiasm for learning was enhanced. Most notable was an increased willingness on the part of the participants to investigate new areas and ways of learning. When the students were given opportunities to combine academic and arts experiences, they were more likely to explore and persist in trying to increase skills in deficit areas.

European Journal of Human Genetics - An atypical 7q11.23 deletion in a normal IQ Williams-Beuren syndrome patient

European Journal of Human Genetics - An atypical 7q11.23 deletion in a normal IQ Williams-Beuren syndrome patient:

"Williams–Beuren syndrome (WBS; OMIM no. 194050) is a multisystemic neurodevelopmental disorder caused by a hemizygous deletion of 1.55 Mb on chromosome 7q11.23 spanning 28 genes. Haploinsufficiency of the ELN gene was shown to be responsible for supravalvular aortic stenosis and generalized arteriopathy, whereas LIMK1, CLIP2, GTF2IRD1 and GTF2I genes were suggested to be linked to the specific cognitive profile and craniofacial features. These insights for genotype–phenotype correlations came from the molecular and clinical analysis of patients with atypical deletions and mice models. Here we report a patient showing mild WBS physical phenotype and normal IQ, who carries a shorter 1 Mb atypical deletion. This rearrangement does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the hypothesis that hemizygosity of the GTF2IRD1 and GTF2I genes might be involved in the facial dysmorphisms and in the specific motor and cognitive deficits observed in WBS patients."

Lions Club comes to the aid of local family with 13 year old Williams Syndrome Girl

Main Street Los Gatos: San Jose Mercury News:

"The Los Gatos Lions Club is raising money to help the family of a local woman who died this week from cancer.

Michelle Hargett Beebee, a graduate of Los Gatos High, was a single working mom, studying to be a teacher, when she was diagnosed in September with stage 4 pancreatic cancer. It was too late for any possible surgical success, and she died Monday at age 43 while in hospice care.

Beebee's parents, Carol and Joe Hargett, will become the primary caregivers for her children, sons Austin, 16, and Alex, 10, and a daughter, Aubrey, 13, who has Williams syndrome, a chromosomal disorder."

Williams Syndrome Music Savant Gloria Lenhoff performs Jewish song "Maoz Tzur- Rock of Ages"

Pioneering Shed Shop fundraiser dies at 79 : Express & Star

Express & Star:

"Pioneering Shed Shop fundraiser dies at 79.

A grandmother who ran a charity shop from the bottom of her garden, raising more than £65,000 over two decades, has died. Pauline Barnett was 79.

Mrs Barnett set up her shop in 1979 in a shed at her home in Needwood Grove, Stone Cross, West Bromwich. It was such a novelty at the time, it attracted bargain hunters from as far afield as Ireland.

The mother of three started selling secondhand clothes to raise money for the Williams Syndrome Foundation. Her son Michael was born with the condition, which causes mental and physical disabilities, and died aged 35."

Summary Statement: What is Williams Syndrome?

Toddler With Elfin Face, Cardiovascular Abnormalities, Hypercalcemia, and Developmental Delays

Here is one doctor's summary analysis of Williams Syndrome.

JAMES S. LEUNG, MD
Hospital for Sick Children, Toronto C. PION KAO, MD

Classically, Williams syndrome presents with transient infantile hypercalcemia that usually resolves by childhood, congenital cardiovascular defects, dysmorphic craniofacial features, a characteristic cognitive and personality profile, growth retardation, and developmental delays.1,2 This multisystem neurodevelopmental disorder was first described by Williams in 1961 and shortly afterward by Beuren (in 1962).3,4 Hence, it is also known as Williams-Beuren syndrome.

INCIDENCE AND ETIOLOGY

The incidence is about 1 in 7500 live births.5 Boys and girls are equally affected.5

Williams syndrome is caused by a hemizygous microdeletion of the ELN gene and contiguous genes on chromosome 7 at band 7q11.23.6,7 This microdeletion results from an unequal meiotic crossover event in one of the parents.8 Deletions of the ELN gene, which encodes for the protein elastin, are found in virtually all patients with Williams syndrome and are directly implicated in the pathogenesis of cardiovascular disease in these patients.6,9,10 However, because ELN is not expressed in significant levels in the brain, ELN deletions are not thought to be responsible for the visuospatial cognition problems, mental retardation, and facial dysmorphology associated with Williams syndrome.11 Instead, these features have been attributed to the combined effects of LIM-K, CYLN2, GTF2IRD1, and GTF2I gene deletions.9,12

Although most cases appear sporadically from de novo mutations, occasional cases of autosomal dominant transmission—occurring when adults with Williams syndrome have children—have been reported.13

CLINICAL MANIFESTATIONS

About 75% of patients have congenital cardiovascular defects, notably supravalvular aortic stenosis (at least 65% of all patients), followed by peripheral pulmonary stenosis (24%) and ventricular septal defects (12%).1 Renal, coronary, mesenteric, cerebral, and carotid artery stenosis may also occur but usually develop in older children and adults.2,10 Renal disease, in particular, needs to be evaluated early because it can lead to renal failure.

The craniofacial phenotype is characterized by mild microcephaly, upturned nostrils, a flat nasal bridge, full lips, wide mouth, long philtrum, bitemporal depressions, periorbital fullness, stellate irides, micrognathia, epicanthal folds, microdontia, malocclusion, enamel hypoplasia, dental aplasia, and fan-shaped orientation of the front teeth (elfin face).1,2

Children with Williams syndrome consistently exhibit a personality profile characterized by highly sociable and overly friendly behaviors accompanied by seemingly paradoxical anxieties, phobias, and poor daily living skills (“cocktail party” personality).14-17 These children have a happy affect—they cheer you up if you are having a bad day in clinic—and remarkable musical ability, which is one of their paradoxical strengths and gives parents hope. Affected children often have mild to moderate mental retardation, extremely severe visuospatial construction problems, and delayed vocabulary acquisition but have normal grammatical, facial recognition, and auditory rote memory skills.14,17 These children tend to be hyperactive (63% to 87% of children) and are 4 times more likely to have attention-deficit/hyperactivity disorder.1,18

Children with Williams syndrome typically exhibit global growth delays during the first few years of life, followed by a period of childhood catch-up growth; however, they ultimately have short stature in adulthood. Many have precocious puberty.1,19

COMPLICATIONS

Cardiovascular disease continues to be a chief concern as persons with Williams syndrome progress into adulthood.20 Many adults report worsening of preexisting supravalvular aortic stenosis.21 Hypertension may develop secondary to renal artery stenosis.20 Myocardial infarction, congestive heart failure, and stroke have also been reported with increased frequency.2 Affected persons are at increased risk for sudden death attributed mainly to coronary artery stenosis or severe biventricular outflow tract obstruction.22,23

Other associated anomalies and complications include gastroesophageal reflux, peptic ulcer disease, diverticulitis, cholelithiasis, bladder calculi, chronic urinary tract infections, premature gray hair, hypothyroidism, esotropia, bilateral inguinal hernias, joint laxity, joint contractures, scoliosis, kyphosis, lordosis, hypotonia, anxiety, and depression.2,18,20,21

DIAGNOSIS

The differential diagnosis of Williams syndrome includes supravalvular aortic stenosis, infantile hypercalcemia, autism, and Down syndrome.13,17,24,25 The unique clinical features of these conditions often allow a straightforward differentiation to be made. However, the diagnosis of Williams syndrome can be delayed because of a lack of significant clinical features during infancy.1

Suspected cases of Williams syndrome can be confirmed cytogenetically. The preferred diagnostic test is fluorescence in situ hybridization.26 In the patient described, results of this test showed a deletion of the ELN gene at 7q11.23.

TREATMENT

Treatment is largely symptomatic and supportive. A multidisciplinary approach is important; the treatment team should include a pediatrician, cardiologist, geneticist, ophthalmologist, neurologist, physiotherapist, psychologist, dentist, schoolteacher, and social worker. Support groups are also available for families (in Canada: the Canadian Association for Williams Syndrome [http://www.caws-can.org]; in the United States: The Williams Syndrome Association [http://www.williamssyndrome. org]).


-----------------------

REFERENCES:
1. Morris CA, Demsey SA, Leonard CO, et al. Natural history of Williams syndrome: physical characteristics. J Pediatr. 1988;113:318-326.

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

3. Williams JC, Barratt-Boyes BG, Lowe JB. Supravalvular aortic stenosis. Circulation. 1961;24:1311-1318.

4. Beuren AJ, Apitz J, Harmjanz D. Supravalvular aortic stenosis in association with mental retardation and certain facial appearance. Circulation. 1962;26: 1235-1240.

5. Strømme P, Bjørnstad PG, Ramstad K. Prevalence estimation of Williams syndrome. J Child Neurol. 2002;17:269-271.

6. Ewart AK, Morris CA, Atkinson D, et al. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet. 1993;5:11-16.

7. Paterson SJ, Schultz RT. Neurodevelopmental and behavioral issues in Williams syndrome. Curr Psychiatry Rep. 2007;9:165-171.

8. Urbán Z, Helms C, Fekete G, et al. 7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover. Am J Hum Genet. 1996;59: 958-962.

9. Osborne L, Pober B. Genetics of childhood disorders, pt 27: genes and cognition in Williams syndrome. J Am Acad Child Adolesc Psychiatry. 2001;40:732-735.

10. Donnai D, Karmiloff-Smith A. Williams syndrome: from genotype through to the cognitive phenotype. Am J Med Genet. 2000;97:164-171.

11. Ashkenas J. Williams syndrome starts making sense. Am J Hum Genet. 1996;59:756-761.

12. Francke U. Williams-Beuren syndrome: genes and mechanisms. Hum Mol Genet. 1999;8:1947-1954.

13. Metcalfe K, Simeonov E, Beckett W, et al. Autosomal dominant inheritance of Williams-Beuren syndrome in a father and son with haploinsufficiency for FKBP6. Clin Dysmorphol. 2005;14:61-65.

14. Mervis CB, Klein-Tasman BP. Williams syndrome: cognition, personality, and adaptive behavior. Ment Retard Dev Disabil Res Rev. 2000;6:148-158.

15. Dykens E. Anxiety, fears and phobias in persons with Williams syndrome. Dev Neuropsychol. 2003;23:291-316.

16. Klein-Tasman BP, Mervis CB. Distinctive personal characteristics of 8-, 9- and 10-year-olds with Williams syndrome. Dev Neuropsychol. 2003;23:269-290.

17. Mervis CB, Becerra AM. Language and communicative development in Williams syndrome. Ment Retard Dev Disabil Res Rev. 2007;13:3-15.

18. Leyfer OT, Woodruff-Borden J, Klein-Tasman BP, et al. Prevalence of psychiatric disorders in 4 to 16-year-olds with Williams syndrome. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:615-622.

19. Partsch CJ, Dreyer G, Gosch A, et al. Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome. J Pediatr. 1999;134:82-89.

20. Howlin P, Udwin O. Outcome in adult life for people with Williams syndrome— results from a survey of 239 families. J Intellect Disabil Res. 2006; 50(pt 2):151-160.

21. Lopez-Rangel E, Maurice M, McGillivray B, Friedman JM. Williams syndrome in adults. Am J Med Genet. 1992;44:720-729.

22. Bird LM, Billman GF, Lacro RV, et al. Sudden death in Williams syndrome: report of ten cases. J Pediatr. 1996;129:926-931.

23. Wessel A, Gravenhorst V, Buchhorn R, et al. Risk of sudden death in the Williams-Beuren syndrome. Am J Med Genet. 2004;127A:234-237.

24. Morris CA, Mervis CB. Williams syndrome and related disorders. Annu Rev Genomics Hum Genet. 2000;1:461-484.

25. Mervis CB, Robinson BF. Expressive vocabulary ability of toddlers with Williams syndrome or Down syndrome: a comparison. Dev Neuropsychol. 2000; 17:111-126.

26. Cagle AP, Waguespack SG, Buckingham BA, et al. Severe infantile hypercalcemia associated with Williams syndrome successfully treated with intravenously administered pamidronate. Pediatrics. 2004;114:1091-1095.

Clarity on Williams Syndrome Causes

What Causes Williams Syndrome?

There are 20,000-25,000 genes in the human genome and Williams syndrome is caused by a deletion of about 25 of them from a specific region on chromosome 7. It is likely that the absence of a few of these genes (not all) causes the problems associated with Williams syndrome. Amongst the genes that are usually missing from affected individuals are CLIP2, ELN, and GTF21.
CLIP2 - codes for a protein called CAP-GLY domain containing linker protein 2; it is believed to play a role in the structure and function of nerve cells.
ELN - codes for a protein called elastin which is a major component of elastin fibres that provide strength and flexibility to connective tissue. Researchers have discovered that absence of ELN is associated with connective tissue problems and cardiovascular abnormalities.
GTF1 - codes for two proteins called BAP-135 and TFII-I. BAP-135 has a role in the immune system and contributes to the activation of B cells in response to foreign invaders. TFII-I is a transcription factor that is active in the brain and other parts of the body. Some scientists think that it is involved in the regulation of calcium into cells. It has also been postulated that loss of the GTF1 gene is associated with the learning disabilities observed in Williams syndrome.
At the time of writing (December 2009) the relationship between many of the deleted genes and Williams syndrome symptoms is unknown.