Williams-Beuren

Williams syndrome Classification and external resources
ICD-10	Q 93.8
ICD-9	758.9
OMIM	194050
MedlinePlus	001116
eMedicine	ped/2439
MeSH	D018980

Williams syndrome (WS; also Williams-Beuren syndrome or WBS) is a rare neurodevelopmental disorder caused by a deletion of about 26 genes from the long arm of chromosome 7.¹ It is characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers, coupled with unpredictably occurring negative outbursts; a predisposition to violent outbursts; mental retardation coupled with unusual (for persons who are diagnosed as mentally retarded) language skills; a love for music; and cardiovascular problems, such as supravalvular aortic stenosis and transient hypercalcaemia. The syndrome was first identified in 1961 by Dr. J. C. P. Williams of New Zealand. ²

Symptoms

Individuals with Williams syndrome are highly verbal and sociable, but lack common sense and typically have low intelligence. The condition has been contrasted with autism, which is characterized by a lack of social interests. Individuals with WS hyper-focus on the eyes of others in social engagements.³ There also appears to be a higher prevalence of left-handedness and left-eye dominance in those with Williams,⁴ and cases of absolute pitch appear to be significantly higher amongst those with the condition.⁵ People with Williams syndrome often have hyperacusis and phonophobia which resembles noise-induced hearing loss, but this may be due to a malfunctioning auditory nerve.⁶⁷ Individuals with Williams syndrome also report higher levels of fears, which may be associated with hyperacusis.⁸

Visual perception

Individuals with Williams syndrome have difficulties with visual processing, but this is related to how complex spatial relationships are rather than issues with depth perception.⁹

Cause

Williams Syndrome genes¹⁰¹¹
ASL · BAZ1B · BCL7B · CLDN3 · CLDN4 CLIP2 · EIF4H · ELN · FZD9 · FKBP6 GTF2I · GTF2IRD1 · HIP1 · KCTD7 LAT2 · LIMK1 · MDH2 · NCF1 NSUN5 · POR · RFC2 · STX1A · TBL2 TRIM50 · TRIM73 · TRIM74 WBSCR14 · WBSCR18 · WBSCR21 WBSCR22 · WBSCR23 · WBSCR24 WBSCR27 · WBSCR28

Williams syndrome is caused by the deletion of genetic material from the region q11.23 of chromosome 7. The deleted region includes more than 20 genes, and researchers believe that the loss of several of these genes probably contributes to the characteristic features of this disorder. CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted in people with Williams syndrome. Researchers have found that loss of the ELN gene, which codes for the protein elastin, is associated with the connective-tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis (SVAS) and supravalvular pulmonary stenosis (SVPS)) found in many people with this syndrome. Studies suggest that deletion of LIMK1, GTF2I, GTF2IRD1, and perhaps other genes may help explain the characteristic difficulties with visual–spatial tasks. Additionally, there is evidence that the loss of several of these genes, including CLIP2, may contribute to the unique behavioral characteristics, learning disabilities, and other cognitive difficulties seen in Williams syndrome.

Management

Guidelines published by the American Academy of Pediatrics include cardiology evaluations, anethesia consultation for any child requiring surgery, developmental and psychoeducational assessment, and many other examination, laboratory, and anticipatory guidance recommendations.¹²

Epidemiology

References

^ ^a ^b Martens MA, Wilson SJ, Reutens DC (2008). "Research Review: Williams syndrome: a critical review of the cognitive, behavioral, and neuroanatomical phenotype". J Child Psychol Psychiatry 49 (6): 576–608. doi:10.1111/j.1469-7610.2008.01887.x. PMID 18489677.
^ Dobbs, David (July 8, 2007). "The Gregarious Brain.", New York Times. Retrieved on 25 September 2007. "If a person suffers the small genetic accident that creates Williams syndrome, he’ll live with not only some fairly conventional cognitive deficits, like trouble with space and numbers, but also a strange set of traits that researchers call the Williams social phenotype or, less formally, the “Williams personality”: a love of company and conversation combined, often awkwardly, with a poor understanding of social dynamics and a lack of social inhibition."
^ Riby DM, Hancock PJ (2008). "Viewing it differently: Social scene perception in Williams syndrome and Autism". Neuropsychologia 46 (11): 2855–60. doi:10.1016/j.neuropsychologia.2008.05.003. PMID 18561959.
^ Van Strien JW, Lagers-Van Haselen GC, Van Hagen JM, De Coo IF, Frens MA, Van Der Geest JN (2005). "Increased prevalences of left-handedness and left-eye sighting dominance in individuals with Williams-Beuren syndrome". J Clin Exp Neuropsychol 27 (8): 967–76. doi:10.1080/13803390490919119. PMID 16207621.
^ Sacks O (May 1995). "Musical ability". Science 268 (5211): 621–2. doi:10.1126/science.7732360. PMID 7732360.
^ Gothelf D, Farber N, Raveh E, Apter A, Attias J (February 2006). "Hyperacusis in Williams syndrome: characteristics and associated neuroaudiologic abnormalities". Neurology 66 (3): 390–5. doi:10.1212/01.wnl.0000196643.35395.5f. PMID 16476938, http://www.neurology.org/cgi/pmidlookup?view=long&pmid=16476938.
^ Johnson LB, Comeau M, Clarke KD (April 2001). "Hyperacusis in Williams syndrome". J Otolaryngol 30 (2): 90–2. doi:10.2310/7070.2001.20811. PMID 11770962.
^ Blomberg S, Rosander M, Andersson G (2006). "Fears, hyperacusis and musicality in Williams syndrome". Res Dev Disabil 27 (6): 668–80. doi:10.1016/j.ridd.2005.09.002. PMID 16269236.
^ Van der Geest JN, Lagers-van Haselen GC, van Hagen JM, et al (October 2005). "Visual depth processing in Williams-Beuren syndrome". Exp Brain Res 166 (2): 200–9. doi:10.1007/s00221-005-2355-1. PMID 15965761.
^ Merla G, Howald C, Henrichsen CN, et al (August 2006). "Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes". Am. J. Hum. Genet. 79 (2): 332–41. doi:10.1086/506371. PMID 16826523.
^ Schubert C, Laccone F (November 2006). "Williams-Beuren syndrome: determination of deletion size using quantitative real-time PCR". Int. J. Mol. Med. 18 (5): 799–806. PMID 17016608, http://www.spandidos-publications.com/ijmm/article.jsp?article_id=ijmm_18_5_799.
^ Committee on Genetics, American Academy of Pediatrics (01 May 2001). "Health care supervision for children with Williams syndrome". Pediatrics 107 (5): 1192–2004. PMID 11331709, http://aappolicy.aappublications.org/cgi/content/full/pediatrics;107/5/1192.

Contents