Manifestaciones clínicas asociadas al síndrome de Prader-Willi: Revisión Descriptiva
Resumen
RESUMEN
El síndrome de Prader–Willi (SPW) es un trastorno genético, que afecta el neurodesarrollo que, a pesar de su baja frecuencia, merece ser considerado como un trastorno de relevancia clínica al ser la causa más frecuente de obesidad de origen genético. Las manifestaciones clínicas que derivan de SPW tienen origen en la desregulación hipotalámica, por lo cual, comprendiendo la trascendencia e implicación de la afectación hipotalámica, puede comprenderse la amplia gama de manifestaciones que pueden presentarse con severidad variable y cuyas complicaciones su vez la afectación a la salud y socialización a largo plazo afectando la calidad de vida de los pacientes con SPW. Un diagnóstico preciso permite distinguir este síndrome de otros trastornos genéticos y de otras patologías que afectan la función hipotalámica a la vez que permite estimar la gravedad de las manifestaciones y el riesgo de repetición en una misma familia. Por ello, la presente revisión descriptiva se ofrece con el objetivo de describir las manifestaciones clínicas del síndrome de Prader-Willi que orienten la sospecha clínica, las similitudes que presenta este síndrome con otros trastornos, así como presentar las técnicas de diagnóstico disponibles que permiten orientar adecuadamente el abordaje de los pacientes y facilitar su manejo integral oportunamente.
ABSTRACT:
Prader-Willi syndrome (PWS) is a genetic disorder that affects neurodevelopment, which, despite its low frequency, deserves to be considered a clinically relevant disorder since it is the most frequent cause of genetically derived obesity. The clinical manifestations that derive from SPW correlate to those from a hypothalamic dysregulation, so that, understanding the importance and implication of the hypothalamic involvement, the wide range of manifestations that can present with variable severity and whose complications in turn affect the health can be understood. and long-term socialization affecting the quality of life of patients with PWS. An accurate diagnosis can discriminate this syndrome from other genetic disorders and from non-genetic pathologies that affect hypothalamic function, while also allowing to estimate the severity in a specific patient and the risk of repetition in other family members. Therefore, the present descriptive review is aimed to describe the clinical manifestations of Prader-Willi syndrome to guide the clinical diagnosis; the signs and symptoms that can differentiate this syndrome from other disorders, as well as presenting a description of the actual diagnostic techniques that can allow a prompt and precise diagnosis, and thus, translate in a comprehensive and timely approach of the patients with PWS.
Referencias
Cassidy S. Genetics of Prader-Willi syndrome. In Greenswag LR, Alexander RC, eds. Management of Prader-Willi syndrome. 2 ed. New York: Springer Verlag; 1959. p. 18. https://ncbi.nlm.nih.gov/pubmed/22237428.
Nicholls RD, Knoll JHM, Butler MG, Karam, S & Lalande, M. Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome. Nature. 1989;342, 281-285. doi:10.1038/342281a0
Ward O. John Langdon Down: the man and the message. Down Syndrome Research and Practice. 1999;6(1):19-24. https://pdfs.semanticscholar.org/ff80/0fd17f5c672ef6596be5e42213d644d121c6.pdf.
Driscoll DJ, Migeon BR. Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations. Somat Cell Mol Genet. 1990;16:267–82. PMID: 1694309.
Bittel DC, Butler MG. Prader–Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med. 2005;7(14):1-20. 10.1017/S1462399405009531. https://www.ncbi.nlm.nih.gov/pubmed/16038620
Polex-Wolf J, Lam BY, Larder R, Tadross J, Rimmington D, Bosch F, et al. Hypothalamic loss of Snord116 recapitulates the hyperphagia of Prader-Willi syndrome. J Clin Investig. 2018;128(3). doi: 10.1172/JCI97007
Bochukova EG, Lawler K, Croizier S, Keogh JM, Patel N, Strohbehn G, et al. A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome. Cell Reports. 2018;22(13):3401-8. doi: https://doi.org/10.1016/j.celrep.2018.03.018.
Prader A. Ein syndrom von adipositas, kleinwuchs, kryptorchismus und oligophrenie nach myatonieartigem zustand im neugeborenenalter. Schweiz Med Wochenschr. 1956;86:1260-1. https://ci.nii.ac.jp/naid/10019494016/
Butler MG, Kimonis V, Dykens E, Gold JA, Miller J, Tamura R, et al. Prader–Willi syndrome and early‐onset morbid obesity NIH rare disease consortium: A review of natural history study. Am J Med Gen Part A. 2018;176(2):368-75. 10.1002/ajmg.a.38582
Rodriguez JA, Zigman JM. Hypothalamic loss of Snord116 and Prader-Willi syndrome hyperphagia: the buck stops here? Journal of Clinical Investigation. 2018;128(3):900-2. https://doi.org/10.1172/JCI97007
Polex-Wolf J, Yeo GS, O’Rahilly S. Impaired prohormone processing: a grand unified theory for features of Prader-Willi syndrome? J Clin Investig. 2017;127(1):98-9. 10.1172/JCI91307
Purtell L, Qi Y, Campbell L, Sainsbury A, Herzog H. Adult-onset deletion of the Prader-Willi syndrome susceptibility gene Snord116 in mice results in reduced feeding and increased fat mass. Transl Pediatr. 2017;6(2):88. 10.21037/tp.2017.03.06
Bakker N, Wolffenbuttel K, Looijenga L, Hokken-Koelega A. Testes in infants with Prader-Willi syndrome: human chorionic gonadotropin treatment, surgery and histology. J Urol. 2015;193(1):291-8. https://doi.org/10.1016/j.juro.2014.07.113
Kalsner L, Chamberlain SJ. Prader-Willi, Angelman, and 15q11-q13 duplication syndromes. Pediatr Clin North Am. 2015;62(3):587-606. https://doi.org/10.1016/j.pcl.2015.03.004
Mejlachowicz D, Nolent F, Maluenda J, Ranjatoelina-Randrianaivo H, Giuliano F, Gut I, et al. Truncating mutations of MAGEL2, a gene within the Prader-Willi locus, are responsible for severe arthrogryposis. Am J Human Genet. 2015;97(4):616-20. https://doi.org/10.1016/j.ajhg.2015.08.010
Pérez L, Muñoz-Ruata J, García E. El Síndrome de Prader-Willi: Características Cognitivas e Implicaciones Educativas. Psicología Educativa. 16(1): 41-50. https://dialnet.unirioja.es/servlet/articulo?codigo=3434919
Holm VA, Cassidy SB, Butler MG, Hanchett JM, Greenswag LR, Whitman BY, et al. Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics. 1993;91(2):398-402. PMID: 8424017
Taboada N, Lardoeyt R. Criterios para el diagnóstico clínico de algunos síndromes genéticos. Rev Cubana de Pediatría. 2003; ene-abr 75(1).
http://scielo.sld.cu/scielo.php?pid=S0034-75312003000100007&script=sci_arttext&tlng=pt
Paterson W, Donaldson M. Growth hormone therapy in the Prader-Willi syndrome. Arch Disease Child. 2003;88(4):283-5. http://dx.doi.org/10.1136/adc.88.4.283.
Dimitropoulos A, Feurer I, Roof E, Stone W, Butler M, Sutcliffe J, et al. Appetitive behavior, compulsivity, and neurochemistry in Prader‐Willi syndrome. Ment Retard Dev Disabil Res Rev. 2000;6(2):125-30. https://doi.org/10.1002/98-2779(000)6:2<125::AID-MRDD6>3.0.CO;2-T
Butler MG, Manzardo AM, Heinemann J, Loker C, Loker J. Causes of death in Prader-Willi syndrome: Prader-Willi Syndrome Association (USA) 40-year mortality survey. Genet Med. 2017;19(6):635. doi: 10.1038/gim.2016.178
Bar C, Diene G, Molinas C, Bieth E, Casper C, Tauber M. Early diagnosis and care is achieved but should be improved in infants with Prader-Willi syndrome. Orphanet journal of rare diseases. 2017;12(1):118. doi.10.1186/s13023-017-0673-6
Kim Y, Lee H-M, Xiong Y, Sciaky N, Hulbert SW, Cao X, et al. Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader–Willi syndrome. Nat Med. 2017;23(2):213. DOI: 10.1038/nm.4257
Angulo M, Butler M, Cataletto M. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J Endocrinol Invest. 2015;38(12):1249-63. doi: 10.1007/s40618-015-0312-9
Ministerio de Trabajo y Asuntos Sociales. El síndrome de prader-Willi, guía para familias y profesionales. 1999, pp. 35-39. Edita: Ministerio de Trabajo y Asuntos Sociales, Secretaría General de Asuntos Sociales, IMSERSO.
www.imserso.es/InterPresent2/groups/imserso/.../356guia_sndrome_prader_Willi.pdf.
Santoro SL, Hashimoto S, McKinney A, Mosher TM, Pyatt R, Reshmi SC, et al. Assessing the Clinical Utility of SNP Microarray for Prader-Willi Syndrome due to Uniparental Disomy. Cytogenetic and genome research. 2017;152(2):105-9. doi:10.1159/000478921
Glenn CC, Saitoh S, Jong MT et al: Gene structure, DNA methylation, and imprinted expression of the human SNRPN gene. Am J Hum Genet 1996; 58: 335– 346. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914536.
Kubota T, Das S, Christian SL, Baylin SB, Herman JG, Ledbetter DH: Methylation-specific PCR simplifies imprinting analysis. Nat Genet 1997; 16: 16–17. https://www.nature.com/articles/ng0597-15.
Estrada H, Fernández L, Rivera C, Grether P. MLPA (Amplificación de sondas dependiente de ligandos múltiples) en el diagnóstico perinatal rápido de las principales aneuploidías. Perinatol Reprod Hum 2012; 26 (3): 172-179 http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0187-53372012000300002.
Thuilleaux D, Laurier V, Copet P, Tricot J, Demeer G, Mourre F, et al. A model to characterize psychopathological features in adults with Prader‐willi syndrome. Am J Med Genet Part A. 2018;176(1):41-7. https://doi.org/10.1002/ajmg.a.38525
Barclay SF, Rand CM, Nguyen L, Wilson RJ, Wevrick R, Gibson WT, et al. ROHHAD and Prader-Willi syndrome (PWS): clinical and genetic comparison. Orphanet Journal of Rare Diseases. 2018;13(1):124. doi:10.1186/s13023-018-0860-0
Grugni G, Crinò A, De Bellis A, Convertino A, Bocchini S, Maestrini S, et al. Autoimmune pituitary involvement in Prader–Willi syndrome: new perspective for further research. Endocrine. 2018:1-4. 10.1186/1687-9856-2013-14
Goldstone A, Holland A, Hauffa B, Hokken-Koelega A, Tauber M, PWS SCatSEMotCCoPW. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metabolism. 2008;93(11):4183-97. https://academic.oup.com/jcem/article/93/11//2627225.
Cassidy SB. Prader-Willi syndrome. Journal of medical genetics. 1997;34(11):917-23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1051120/pdf/jmedgene00253-0037.pdf.
Tauber, M., Diene, G., & Molinas, C. (2016). Sequelae of GH Treatment in Children with PWS. Pediatr Endocrinol Rev 14(2), 138. https://www.ncbi.nlm.nih.gov/pubmed/28508607.
Grugni G, Sartorio A, Crinò A. Growth hormone therapy for Prader–Willi syndrome: challenges and solutions. Ther Clin Risk Manag. 2016;12: 873-881. https://www.ncbi.nlm.nih.gov/pubmed/27330297.
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