Envelhecimento precoce pode estar relacionado com a Síndrome de Williams?
Barra lateral de artigos
Conteúdo do artigo principal
Resumo
Introdução: A síndrome de Williams (SW) é condição genética rara, autossômica dominante causada por uma microdeleção heterozigótica em 7q11.23. Apresenta manifestações clínicas diversas, incluindo sintomas de envelhecimento precoce multissistêmicos, como o desenvolvimento precoce de doenças de idades mais avançadas. A haploinsuficiência do gene ELN, o estresse oxidativo, desencadeado pela superexpressão do gene NCF1 e disfunção mitocondrial, são apontados como responsáveis por manifestações ligadas ao envelhecimento.
Objetivo: Analisar aspectos clínicos e biológicos da síndrome de Williams relacionados ao envelhecimento precoce, buscando entender suas causas e mecanismos de ação.
Método: Trata-se de revisão narrativa, sendo utilizados 25 artigos obtidos nas bases de dados Scielo, PubMed, ProQuest e Google Acadêmico. Foram incluídos estudos publicados entre 1996 e 2024, nos idiomas português e inglês, utilizando os descritores “síndrome de Williams”, “envelhecimento”, “NCF1” e “ELN”.
Resultado: Haploinsuficiência do gene ELN, aumento da angiotensina II, superexpressão do gene NCF1 e alterações na respiração celular mitocondrial nos portadores da síndrome de Williams geram estresse oxidativo, e consequentemente, envelhecimento precoce nos afetados. Os portadores da síndrome podem apresentar perda auditiva, puberdade e catarata precoces e desenvolvimento cognitivo prejudicado, manifestando transtorno de déficit de atenção e ansiedade.
Conclusão: O envelhecimento precoce na síndrome de Williams envolve manifestações multissistêmicas associadas à haploinsuficiência do gene ELN e à superexpressão do gene NCF1, que promovem estresse oxidativo e disfunção celular.
Detalhes do artigo
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Referências
Rech A, Rinaldi IC, Marega T. Restorative treatment in patient with Williams Syndrome: case report. Revista Gaúcha de Odontologia. 2022;70:e20220026. https://doi.org/10.1590/1981-86372022002620200155
Michele Moreira Nunes. Avaliação do funcionamento cognitivo de pacientes com Síndrome de Williams-Beuren. 2011
Stanley TL, Leong AL, Pober BR. Growth, Body Composition, and Endocrine Issues in Williams Syndrome. Current Opinion in Endocrinology, Diabetes & Obesity. 2021;28(1):64-74. https://doi.org/10.1097/med.0000000000000588.
Kozel BA, Barak B, Kim CA, Mervis CB, Osborne LR, Porter M, et al. Williams Syndrome. Nature Reviews Disease Primers. 2021;7(1):42. https://doi.org/10.1038/s41572-021-00276-z.
Morris CA, Braddock SR, Council on Genetics. Health Care Supervision for Children With Williams Syndrome. Pediatrics. 2020;145(2):e20193761. https://doi.org/10.1542/peds.2019-3761
Ferrari M, Stagi S. Oxidative Stress in Down and Williams-Beuren Syndromes: An Overview. Molecules. 2021;26(11):3139. https://doi.org/10.3390/molecules26113139
Del Campo M, Antonell A, Magano LF, Muñoz FJ, Flores R, Bayés M, et al. Hemizygosity at the NCF1 Gene in Patients with Williams-Beuren Syndrome Decreases Their Risk of Hypertension. The American Journal of Human Genetics. 2006;78(4):533–42. https://doi.org/10.1086/501073
ELN gene: MedlinePlus Genetics. medlineplus.gov. Available from: https://medlineplus.gov/genetics/gene/eln/
Krinsky-McHale SJ, Kittler P, Brown WT, Jenkins EC, Devenny DA. Repetition Priming in Adults With Williams Syndrome: Age-Related Dissociation Between Implicit and Explicit Memory. American Journal on Mental Retardation. 2005;110(6):482-96. https://doi.org/10.1352/0895-8017(2005)110[482:rpiaww]2.0.co;2
MedlinePlus. Williams syndrome: MedlinePlus Genetics. medlineplus.gov. 2022. Available from: https://medlineplus.gov/genetics/condition/williams-syndrome/
Topázio BA. Estudo genético e clínico da Síndrome de Williams-Beuren em pacientes do nordeste brasileiro. Ibict.br. 2016. Available from: https://bdtd.ibict.br/vufind/Record/UFBA-2_15ea9b3c1b1eb962577bbb676f7d7ae7
Sauna‐aho O, Bjelogrlic‐Laakso N, Sirén A, Kangasmäki V, Arvio M. Cognition in adults with Williams syndrome—A 20‐year follow‐up study. Molecular Genetics & Genomic Medicine. 2019;7(6):e695. https://doi.org/10.1002/mgg3.695
Gagliardi C, Martelli S, Burt MD, Borgatti R. Evolution of Neurologic Features in Williams Syndrome. Pediatric Neurology. 2007;36(5):301–6. https://doi.org/10.1016/j.pediatrneurol.2007.01.001
Elison S, Stinton C, Howlin P. Health and social outcomes in adults with Williams syndrome: Findings from cross-sectional and longitudinal cohorts. Research in Developmental Disabilities. 2010;31(2):587–99. https://doi.org/10.1016/j.ridd.2009.12.013
Pober BR, Morris CA. Diagnosis and management of medical problems in adults with Williams–Beuren syndrome. American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 2007;145C(3):280–90. https://doi.org/10.1002/ajmg.c.30139
Bódizs R, Gombos F, Gerván P, Szőcs K, Réthelyi JM, Kovács I. Aging and sleep in Williams syndrome: Accelerated sleep deterioration and decelerated slow wave sleep decrement. Research in Developmental Disabilities. 2014;35(12):3226–35. https://doi.org/10.1016/j.ridd.2014.07.056
Axelsson EL, Hill CM, Sadeh A, Dimitriou D. Sleep problems and language development in toddlers with Williams syndrome. Research in Developmental Disabilities. 2013;34(11):3988–96. https://doi.org/10.1016/j.ridd.2013.08.018
Cherniske EM, Carpenter TO, Klaiman C, Young E, Bregman J, Insogna K, et al. Multisystem study of 20 older adults with Williams syndrome. American Journal of Medical Genetics. 2004;131A(3):255–64. https://doi.org/10.1002/ajmg.a.30400
Micangeli G, Menghi M, Profeta G, Tarani F, Mariani A, Petrella C, et al. The Impact of Oxidative Stress on Pediatrics Syndromes. Antioxidants. 2022;11(10):1983–3. https://doi.org/10.3390/antiox11101983
Shek N, Choy AM, Lang CC, Miller BE, Tal-Singer R, Bolton CE, et al. Accelerated elastin degradation by age-disease interaction: a common feature in age-related diseases. NPJ Aging. 2024;10(1):1–4. https://doi.org/10.1038/s41514-024-00143-7
Duque Lasio ML, Kozel BA. Elastin-driven genetic diseases. Matrix Biology. 2018;71-72:144–60. https://doi.org/10.1016/j.matbio.2018.02.021
Brengle BM, Lin M, Roth RA, Jones KD, Wagenseil JE, Mecham RP, et al. A new mouse model of elastin haploinsufficiency highlights the importance of elastin to vascular development and blood pressure regulation. Matrix Biology. 2023;117:1–14. https://doi.org/10.1016/j.matbio.2023.02.003
Kozel BA, Danback JR, Waxler JL, Knutsen RH, de las Fuentes L, Reusz GS, et al. Williams Syndrome Predisposes to Vascular Stiffness Modified by Antihypertensive Use and Copy Number Changes in NCF1. Hypertension. 2014;63(1):74–9. https://doi.org/10.1161/hypertensionaha.113.02087
Raimondi F, Siow KM, Wrona D, Fuster-García C, Pastukhov O, Schmitz M, et al. Gene editing of NCF1 loci is associated with homologous recombination and chromosomal rearrangements. Communications Biology. 2024;7(1):1291. https://doi.org/10.1038/s42003-024-06959-z
Pezet M, Jacob MP, Escoubet B, Gheduzzi D, Tillet E, Perret P, et al. Elastin Haploinsufficiency Induces Alternative Aging Processes in the Aorta. Rejuvenation research. 2008;11(1):97–112. https://doi.org/10.1089/rej.2007.0587