ABC News Report (20/20) on Williams Syndrome (in two parts)

A preliminary study of orbitofrontal activation and hypersociability in Williams Syndrome

SpringerLink - Journal Article

"Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. Methods: We performed an event-related functional magnetic resonance imaging study while individuals with WS and typically developing controls (TD) matched positive and negative emotional faces. WS compared to TD showed reduced right amygdala activation during presentation of negative faces, as in the previous literature. In addition, WS showed a unique pattern of right orbitofrontal cortex activation. While TD showed medial orbitofrontal cortex activation in response to positive, and lateral orbitofrontal cortex activation to negative, WS showed the opposite pattern. In light of the general notion of a medial/lateral gradient of reward/punishment processing in the orbitofrontal cortex, these findings provide an additional biological explanation for, or correlate of positive attribution bias and hypersociability in WS."

Navigation ability may be linked to genes according to study with Williams Syndrome subjects

Navigation ability may be linked to genes | Machines Like Us: "In the study, Landau's team challenged people with Williams syndrome to watch while someone hid an object beneath a small cloth flap in one corner of a small rectangular room with four solid black walls that had no landmarks. Subjects were then blindfolded and spun around (think 'Pin the Tail on the Donkey') for about 10 seconds to disorient them. Once the blindfold was taken off, the subjects were asked to find the hidden object.

According to Landau, the people with Williams syndrome searched the four corners randomly; indicating that their ability to mentally visualize the layout of the room and quickly find which corner held the hidden object is severely impaired.

'They searched the room for the hidden object randomly, as if they had never before seen the overall geometry of the room or the lengths of the walls and their geometric – left and right – relation to each other,' Landau explained. 'If they could imagine the overall shape of the room's layout – that there are four walls, two of them long and two of them short and that the toy was hidden in a corner that has a short wall on the right and the long wall on the left – then they should have guessed that one of the two 'geometrically equivalent corners' was the right place. This is what typically developing humans do, as early as 18 months of age.'

Control subjects (healthy college-aged students) responded more typically, searching for the object in one of the two geometrically equivalent corners, as has been found in studies by many other investigators.

According to Landau, the results of this study provides another clue to the link between how genes work, how brains develop and become specialized and what can go wrong to result in very basic cognitive system malfunctioning.

'Although we are quite far from understanding the links between the specific genes that are missing in Williams syndrome and the behavior they show, such as failure to reorient, it is clear that the missing genes ultimately have some effect on the brain,' she said. 'Our evidence is the first to directly show a sub

stantial deficit in this reorientation system that is caused by missing genes in humans.'"

Attentional characteristics of infants and toddlers with Williams syndrome...

Attentional characteristics of infants and toddlers with Williams syndrome … - LooKPDF.com:

"Two studies were conducted to consider the looking behavior of infants and toddlers with Williams syndrome (WS). In Study 1, the looking behavior of a 10-month-old girl with WS during play sessions with her mother and with a stranger was compared to that of 2 groups of infants who were developing normally (ND), 1 matched for chronological age and the other for developmental age. The infant with WS spent more than twice as much time looking at her mother as the infants in either contrast group did. She also spent twice as much time looking at the stranger. In addition, during 78% of this time, her gaze at the stranger was coded as extremely intense. Looks of this intensity were virtually never made by the ND infants."

Williams Syndrome: It's Not a Fairy Tale : NPR

Williams Syndrome: It's Not a Fairy Tale : NPR

Follow the link for the full NPR interview which includes Jeremy Vest.

Summary Article on Williams Syndrome

NEJM -- Williams-Beuren Syndrome

The January 2010 issue of the New England Journal of Medicine has an excellent summary article on Williams Syndrome. A free 21 day trial membership can be started to download the entire article in pdf format.

"Williams–Beuren syndrome (also known as Williams' syndrome; Online Mendelian Inheritance in Man [OMIM] number, 194050), a multisystem disorder, is caused by deletion of the Williams–Beuren syndrome chromosome region, spanning 1.5 million to 1.8 million base pairs and containing 26 to 28 genes. Exactly how gene loss leads to the characteristic phenotype of Williams–Beuren syndrome is unknown, but hypoexpression of gene products is likely to be involved. Estimated to occur in approximately 1 in 10,000 persons,¹ Williams–Beuren syndrome is a microdeletion disorder, or contiguous-gene-deletion disorder, that can serve as a model for the study of genotype–phenotype correlations and potentially reveal . . ."

Comprehension of spatial language in Williams syndrome: Evidence for impaired spatial representation of verbal descriptions; Clinical Linguistics & Phonetics - 21(9):Pages 689-704 - Informa Healthcare

Comprehension of spatial language in Williams syndrome: Evidence for impaired spatial representation of verbal descriptions; Clinical Linguistics & Phonetics - 21(9):Pages 689-704 - Informa Healthcare:

"Results demonstrated that individuals with Williams syndrome were selectively impaired on the second task relative to controls. The study therefore provides support for previous work demonstrating impaired comprehension of spatial language in this population. Furthermore, the results suggest that such impairments reflect a fundamental problem with processing spatial descriptions rather than merely a poor understanding of the semantics of spatial terms, which in turn has implications for the interaction between spatial abilities and language processing in general."

Comprehension of metaphor and metonymy in children with Williams syndrome

Comprehension of metaphor and metonymy in children with Williams syndrome:

"Metonyms may be part of vocabulary and treated as synonyms in Williams syndrome, while metaphor engages additional cognitive mechanisms outside language that develop atypically in this disorder. Despite earlier reports that emphasize good language skills, the Williams syndrome language system shows anomalies compared with typical development."

Numerical abilities in Williams syndrome

Numerical abilities in Williams syndrome: Dissociating the analogue magnitude system and verbal retrieval - Journal of Clinical and Experimental Neuropsychology:

"Two numerical systems—the analogue magnitude system and verbal retrieval—were investigated in Williams syndrome (WS) with three numerical tasks: simple addition, simple multiplication, and number comparison. A new matching technique was introduced in selecting the proper control groups. The WS group was relatively fast in the addition and multiplication tasks, but was slow in number comparison. No reverse numerical effect was observed in the comparison task, and the distance effect was stronger than that in the control groups. The findings indicate a profile with an impaired analogue magnitude system and less impaired verbal retrieval in Williams syndrome."

Books on Williams Syndrome

WS Reference Page:

Anna Pendrak has a great site with this list of books on WS:

"Books on Williams Syndrome

* Fulfilling Dreams - The WS Parent Handbook
* Journey from Cognition to Brain to Gene: Perspectives from Williams Syndrome
* Language Availabilities in Williams Syndrome (Neurocognitive Developments and Impairments)
* The (Strangest) Song: One Father's Quest to Help His Daughter Find Her Voice
* The Official Parent's Sourcebook on Williams Syndrome: A Revised and Updated Directory for the Internet Age
* Understanding Williams Syndrome: Behavioral Patterns and Interventions
* Variability of the Cranial And Dental Phenotype in William's Syndrome
* Williams Syndrome - A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers
* Williams Syndrome Across Languages (Language Acquisition and Language Disorders)
* Williams Syndrome: A Special Double Issue of developmental Neuropsychology (Developmental Neuropsychology)
* Williams Syndrome: Approaches to Intervention
* Williams-Beuren Syndrome: Research, Evaluation, and Treatment"

Complex grammar in Williams syndrome - Clinical Linguistics & Phonetics

Complex grammar in Williams syndrome - Clinical Linguistics & Phonetics:

"This study investigated knowledge of binding and raising in two groups of children with Williams syndrome (WS), 6-12 and 12-16-years-old, compared to typically developing (TD) controls matched on non-verbal MA, verbal MA, and grammar. In typical development, difficulties interpreting pronouns, but not reflexives, persist until the age of around 6, while raising is not mastered until about the age of 8 or 9. If grammar in WS is delayed, but develops in a fashion parallel to TD population, similar patterns of difficulties may be expected, although it has not been established whether the grammatical development is ever complete in the individuals with this disorder. Knowledge of the principle of binding which states that a reflexive must have a c-commanding antecedent, was found to be intact in all the participants, in line with previous reports in the literature. In contrast, children with WS younger than 12 showed a poorer performance on personal pronouns, like two groups of younger matched TD controls, suggesting a previously unreported delay in the acquisition of constraints regulating coreferential interpretation of pronouns. Both groups of children with WS showed an extremely limited comprehension of raised, as opposed to unraised structures. The revealed patterns indicate that, like in unimpaired populations, different aspects of grammar mature at distinct stages of language development in WS: reflexive binding is acquired earlier than constraints governing coreference. However, development of raising seems exceptionally delayed, and perhaps even unattainable, as data from several adults with WS studied in Perovic and Wexler (2006) show. If, as hypothesized by Hirsch and Wexler, the late development of raising is related in TD children to lack of maturation of the knowledge of A-chains or defective phases, it seems reasonable to hypothesize that the even later development of these structures in WS is related to an even later (if ever) maturation of the knowledge of these grammatical forms."

University of Wisconsin Williams Syndrome Lecture

Events, Williams Syndrome and Duplication of the Williams Syndrome Region: Cognition, Language, and Psychopathology, University of Wisconsin School of Medicine and Public Health:

"Williams Syndrome and Duplication of the Williams Syndrome Region: Cognition, Language, and Psychopathology

Date:
4/23/2010

Time:
Noon-1:15pm

Location:
Waisman Center, John D. Wiley Conference Center (Room T216)

1500 Highland Ave.
Madison, WI 53705

For more information:

See the Waisman Center Web Site or contact Teresa Palumbo at (608) 263-5837 or palumbo@waisman.wisc.edu.

John D. Wiley Seminar Series with Carolyn B. Mervis, PhD, Professor, Department of Psychological and Brain Sciences, University of Louisville."

The iris in Williams syndrome.

The iris in Williams syndrome.:

"Forty three children with Williams syndrome and 124 control subjects had their eyes photographed. The photographs were examined by three ophthalmologists and four geneticists of varying experience. A stellate pattern was noted more often in the irides of patients with Williams syndrome (51%) than in those of the control subjects (12%), and was more difficult to detect, or was absent, in heavily pigmented irides. We conclude that the stellate pattern is of diagnostic importance, particularly if the pattern is carefully defined and the clinician is experienced."

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."

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."

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]).


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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.

Covert processing of facial expressions by people with Williams syndrome

Covert processing of facial expressions by people with Williams syndrome:

"Although individuals with Williams Syndrome (WS) are empathic and sociable and perform relatively well on face recognition tasks, they perform poorly on tasks of facial expression recognition. The current study sought to investigate this seeming inconsistency. Participants were tested on a Garner-type matching paradigm in which identities and expressions were manipulated simultaneously as the relevant or irrelevant dimensions. Performance of people with WS on the expression-matching task was poor and relied primarily on facilitation afforded by congruent identities. Performance on the identity matching task came close to the level of performance of matched controls and was significantly facilitated by congruent expressions. We discuss potential accounts for the discrepant processing of expressions in the task-relevant (overt) and task-irrelevant (covert) conditions, expanding on the inherently semantic-conceptual nature of overt expression matching and its dependence on general cognitive level."

Early screenings can help children later in life

Updated: Early screenings can help children later in life | tallahassee.com | Tallahassee Democrat:

"Jeremy Richard was born with Williams syndrome, a rare genetic disorder of the heart that doctors said can generally lead to problems with development.

His mother, Allison Tant, knew physical and cognitive delays were most likely in Jeremy’s future, but it was the screening process when he was just 5-months-old that set her on the right path of therapies and interventions that now allow the 11-year-old to play the piano, guitar and be a successful fourth-grader who is able to function with his learning disabilities."