Williams syndrome (WS) is a developmental disorder affecting connective tissue and the central nervous system. A common feature of WS, supravalvular aortic stenosis, is also a distinct autosomal dominant disorder caused by mutations in the elastin gene. In this study, we identified hemizygosity at the elastin locus using genetic analyses in four familial and five sporadic cases of WS. Fluorescent in situ hybridization and quantitative Southern analyses confirmed these findings, demonstrating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and implicate elastin hemizygosity in the pathogenesis of the disease.

Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome

There are limited population-based data on the occurrence of Williams syndrome. We estimated its prevalence combining data from two investigations. One was an epidemiologic study originally designed to assess the prevalence and etiology of mental retardation among 30,037 Norwegian children born between 1980 and 1985 and living in Akershus County on January 1, 1993. The other investigation was a national survey of Williams syndrome. In the first study, 213 children were referred for evaluation, whereas the second study comprised 57 cases with Williams syndrome born between 1970 and 1992, who were referred for evaluation from all Norwegian counties. The epidemiologic study revealed three children with Williams syndrome, whereas one additional case complying with our demographic criteria was identified in the national survey, thus giving a prevalence of 1 in 7500. In all cases, a typical chromosome 7q11.23 deletion was detected. We also conclude that Williams syndrome is not an uncommon cause of mental retardation, with a prevalence of approximately 6% of patients with genetic etiology.

Prevalence Estimation of Williams Syndrome

Williams–Beuren syndrome, a multisystem disorder caused by the deletion of a chromosome region of 1.5 million to 1.8 million base pairs containing 26 to 28 genes, is a disorder of microdeletion or contiguous gene deletion. This review covers current understanding of the biology of this disorder.

https://www.nejm.org/doi/pdf/10.1056/NEJMra0903074

Williams–Beuren Syndrome

https://www.cell.com/cell/pdf/S0092-8674(00)80077-X.pdf

LIM-kinase1 Hemizygosity Implicated in Impaired Visuospatial Constructive Cognition

Studies of abnormal populations provide a rare opportunity for examining relationships between cognition, genotype and brain neurobiology, permitting comparisons across these different levels of analysis. In our studies, we investigate individuals with a rare, genetically based disorder called Williams syndrome (WMS) to draw links among these levels. A critical component of such a cross-domain undertaking is the clear delineation of the phenotype of the disorder in question. Of special interest in this paper is a relatively unexplored unusual social phenotype in WMS that includes an overfriendly and engaging personality. Four studies measuring distinct aspects of hypersocial behavior in WMS are presented, each probing specific aspects in WMS infants, toddlers, school age children, and adults. The abnormal profile of excessively social behavior represents an important component of the phenotype that may distinguish WMS from other developmental disorders. Furthermore, the studies show that the profile is observed across a wide range of ages, and emerges consistently across multiple experimental paradigms. These studies of hypersocial behavior in WMS promise to provide the groundwork for crossdisciplinary analyses of gene–brain–behavior relationships.

http://lcn.salk.edu/publications/JCNS%20&%20SFN/II%20Jones_JCNS_ChII_2000.pdf

II. Hypersociability in Williams Syndrome

Natural history of Williams syndrome: Physical characteristics

Reports of adults with Williams syndrome (WS) have been rare. We have evaluated 13 adult WS patients and reviewed 16 case reports of WS in patients older than age 16 years. Adults in our study had progressive multisystem medical problems. Cardiovascular complications were common (12/13) including hypertension (8), supravalvular aortic stenosis (9), aortic hypoplasia (3), pulmonic artery stenosis (4), peripheral stenoses (3), and mitral valve prolapse (2). Joint limitation (12/13) was progressive, often accompanied by kyphoscoliosis and lordosis. Recurrent urinary tract infections in 6 individuals led to radiologic studies showing urethral stenosis in 2, and bladder diverticula and vesicoureteral reflux in 3. Gastrointestinal problems included obesity (5), chronic constipation (7), diverticulosis (3), and cholelithiasis (4). Hypercalcemia was documented in 5 patients, although others had hypercalcemic symptoms (abdominal pain, polyuria, and constipation). One 45-year-old man had parathyroid hyperplasia. Previous reports likewise document significant morbidity. Thus, Williams syndrome in an adult appears to dictate aggressive evaluation and monitoring. Investigation of calcium metabolism should be undertaken in each adult WS patient.

Susan A. Demsey

Papers

Natural history of Williams syndrome: Physical characteristics

Adults with Williams syndrome.