Williams syndrome

Autor(es)

Kozel, Beth A. ^[1] ; Barak, Boaz ^{[2, 3]} ; Kim, Chong Ae ^[4] ; Mervis, Carolyn B. ^[5] ; Osborne, Lucy R. ^[6] ; Porter, Melanie ^[7] ; Pober, Barbara R. ^{[8, 9]}

Afiliação do(s) autor(es)

^[1] NHLBI, Translat Vasc Med Branch, NIH, Bldg 10, Bethesda, MD 20892 - USA

^[2] Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv - Israel

^[3] Tel Aviv Univ, Sch Psychol Sci, Tel Aviv - Israel

^[4] Univ Sao Paulo, Dept Paediat, Sao Paulo - Brazil

^[5] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 - USA

^[6] Univ Toronto, Dept Med, Toronto, ON - Canada

^[7] Macquarie Univ, Dept Psychol, Sydney, NSW - Australia

^[8] Harvard Med Sch, Boston, MA 02115 - USA

^[9] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 - USA

• Tipo de documento: Artigo Científico
• Fonte: NATURE REVIEWS DISEASE PRIMERS; v. 7, n. 1 JUN 17 2021.
• Citações Web of Science: 0

Resumo

Williams syndrome is a rare genetic disorder caused by the microdeletion of a region of chromosome 7q11.23. In this Primer, Pober and colleagues provide an overview of the epidemiology, genetic aetiology, diagnosis, common manifestations and management of this syndrome as well as of how quality of life is affected in individuals with Williams syndrome and their families. Williams syndrome (WS) is a relatively rare microdeletion disorder that occurs in as many as 1:7,500 individuals. WS arises due to the mispairing of low-copy DNA repetitive elements at meiosis. The deletion size is similar across most individuals with WS and leads to the loss of one copy of 25-27 genes on chromosome 7q11.23. The resulting unique disorder affects multiple systems, with cardinal features including but not limited to cardiovascular disease (characteristically stenosis of the great arteries and most notably supravalvar aortic stenosis), a distinctive craniofacial appearance, and a specific cognitive and behavioural profile that includes intellectual disability and hypersociability. Genotype-phenotype evidence is strongest for ELN, the gene encoding elastin, which is responsible for the vascular and connective tissue features of WS, and for the transcription factor genes GTF2I and GTF2IRD1, which are known to affect intellectual ability, social functioning and anxiety. Mounting evidence also ascribes phenotypic consequences to the deletion of BAZ1B, LIMK1, STX1A and MLXIPL, but more work is needed to understand the mechanism by which these deletions contribute to clinical outcomes. The age of diagnosis has fallen in regions of the world where technological advances, such as chromosomal microarray, enable clinicians to make the diagnosis of WS without formally suspecting it, allowing earlier intervention by medical and developmental specialists. Phenotypic variability is considerable for all cardinal features of WS but the specific sources of this variability remain unknown. Further investigation to identify the factors responsible for these differences may lead to mechanism-based rather than symptom-based therapies and should therefore be a high research priority. (AU)

• Processo FAPESP: 19/21644-0 - Impacto de variantes genéticas na estabilidade do genoma e seus efeitos no fenótipo
• Beneficiário: Maria Isabel de Souza Aranha Melaragno
• Modalidade de apoio: Auxílio à Pesquisa - Temático