Amal A,
Sreelekshmy B S,
Ranjana S R,
Shaiju S Dharan,
- Assistant Professor Department of Pharmacy Practice, Ezhuthachan College of Pharmaceutical Sciences Kerala India
- Pharm D Intern Department of Pharmacy Practice, Ezhuthachan College of Pharmaceutical Sciences Kerala India
- Pharm D Intern Department of Pharmacy Practice, Ezhuthachan College of Pharmaceutical Sciences Kerala India
- Principal/ HOD Department of Pharmacy Practice, Ezhuthachan College of Pharmaceutical Sciences Kerala India
Abstract
Prader-Willi syndrome (PWS) is a genetic disorder with multisystem involvement, caused by the lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region from paternal 15q11-q13 deletions (about 60%) or maternal uniparental disomy 15 or both. It is a complex and contiguous gene disorder which affects the multiple systems with many clinical presentations especially hypothalamic insufficiency. The clinical features are characterized by short stature position, developmental delay, cognitive and behavioral disorders. The major causes of morbidity and mortality in PWS individuals are obesity and behavioral problems. Specific diagnostic criteria for PWS are both the methylation analysis and the oligo-SNP combination array (OSA). Early diagnosis is needed for the effective management. There is no cure with a single intervention. Management is symptomatic, which includes hormone replacement therapies, behavioral management, control of food intake and patient education. Currently, there were no approved therapy for the management of hyperphagia in PWS. Usually PWS is identified in infancy by genetic test. The genomic changes loss of expression of the genes on chromosomes 15q11.2-q13 through loss of failure of expression. DNA methylation analysis is a powerful tool to access paternal-only, maternal-only or biparental inheritance. This analysis helps to identify the deletion in the majority of individuals with PWS. Another diagnostic option for PWS is Microsatellite analysis. Nutritional counselling for long term weight management is necessary to prevent the inappropriate weight gain, which begin at the age between 1-3years. Growth hormone replacement therapy improves growth and ultimate height, muscle function and level of activity. Psychological and psychosocial considerations are essential for PWS.
Keywords: Prader- willi syndrome, hypogonadism, obesity, genetic mutation, hyperphagia.
References
1. Muscogiuri G, Barrea L, Faggiano F, Maiorino MI, Parrillo M, Pugliese G, Ruggeri RM, Scarano E, Savastano S, Colao A, RESTARE. Obesity in Prader–Willi syndrome: Physiopathological mechanisms, nutritional and pharmacological approaches. Journal of Endocrinological Investigation. 2021; 44(10):2057-70.
2. Cassidy SB, Schwartz S, Miller JL, Driscoll DJ. Prader-willi syndrome. Genetics in medicine. 2012; 14(1):10-26.
3. Butler MG, Miller JL, Forster JL. Prader-Willi syndrome-clinical genetics, diagnosis and treatment approaches: an update. Current pediatric reviews. 2019; 15(4):207-44.
4. Curfs LM, Verhulst FC, Fryns JP. Behavioral and emotional problems in youngsters with Prader-Willi syndrome. Genetic Counseling (Geneva, Switzerland). 1991; 2(1):33-41.
5. Lewis BA, Freebairn L, Heeger S, Cassidy SB. Speech and language skills of individuals with Prader-Willi syndrome. American Journal of Speech-Language Pathology 2002;11(3):258-294.
6. Elena G, Bruna C, Benedetta M, Stefania DC, Giuseppe C. Prader-Willi syndrome: clinical aspects. Journal of obesity; 2012.(1):473941. https://doi.org/10.1155/2012/473941
7. 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. Genetics in Medicine. 2017; 19(6):635-42.
8. Manzardo AM, Loker J, Heinemann J, Loker C, Butler MG. Survival trends from the Prader–Willi syndrome association (USA) 40-year mortality survey. Genetics in Medicine. 2018; 20(1):24-30.
9. Cassidy SB, Driscoll DJ. Prader–willi syndrome. Eur J Hum Genet. 2009; 17(1):3-13. https://doi.org/10.1038/ejhg.2008.165
10. Miller JL, Lynn CH, Driscoll DC, Goldstone AP, Gold JA, Kimonis V, Dykens E, Butler MG, Shuster JJ, Driscoll DJ. Nutritional phases in Prader–Willi syndrome. American journal of medical genetics Part A. 2011; 155(5):1040-9. https://doi.org/10.1002/ajmg.a.33951
11. Butler MG, Lee PD, Whitman BY, editors. Management of Prader-Willi Syndrome. Springer Nature; New York, 2006.
12. Gross N, Rabinowitz R, Gross‐Tsur V, Hirsch HJ, Eldar‐Geva T. Prader–Willi syndrome can be diagnosed prenatally. American Journal of Medical Genetics Part A. 2015; 167(1):80-5.
13. Lee J, Isojima T, Chang MS, Kwun YH, Huh R, Cho SY, Sohn YB, Jin DK. Disease‐specific growth charts for Korean infants with Prader–Willi syndrome. American Journal of Medical Genetics Part A. 2015; 167(1):86-94.
14. Rosenbloom ST, Butler MG. Development and implementation of electronic growth charts for infants with Prader–Willi syndrome. American Journal of Medical Genetics Part A. 2012; 158(11):2743-9.
15. Crino A, Schiaffini R, Ciampalini P, Spera S, Beccaria L, Benzi F, Bosio L, Corrias A, Gargantini L, Salvatoni A, Tonini G. Hypogonadism and pubertal development in Prader-Willi syndrome. European journal of pediatrics. 2003; 162:327-33.
16. Tauber M, Hoybye C. Endocrine disorders in Prader-Willi syndrome: a model to understand and treat hypothalamic dysfunction. The Lancet Diabetes & Endocrinology. 2021; 9(4):235-46.
17. Noordam C, Höybye C, Eiholzer U. Prader–willi syndrome and hypogonadism: A review article. International Journal of Molecular Sciences. 2021; 22(5):2705.
18. Butler JV, Whittington JE, Holland AJ, Boer H, Clarke D, Webb T. Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study. Developmental medicine and child neurology. 2002; 44(4):248-55.
19. Schwartz L, Caixàs A, Dimitropoulos A, Dykens E, Duis J, Einfeld S, Gallagher L, Holland A, Rice L, Roof E, Salehi P. Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium. Journal of Neurodevelopmental Disorders. 2021; (13): article number 25:1-3.
20. Steinhausen HC, Eiholzer U, Hauffa BP, Malin Z. Behavioural and emotional disturbances in people with Prader–Willi syndrome. Journal of Intellectual Disability Research. 2004; 48(1):47-52.
21. Nixon GM, Brouillette RT. Sleep and breathing in Prader‐Willi syndrome. Pediatric pulmonology. 2002; 34(3):209-17.
22. Yee BJ, Buchanan PR, Mahadev S, Banerjee D, Liu PY, Phillips C, Loughnan G, Steinbeck K, Grunstein RR. Assessment of sleep and breathing in adults with prader-willi syndrome: a case control series. Journal of Clinical Sleep Medicine. 2007; 3(7):713-8.
23. Glenn CC, Driscoll DJ, Yang TP, Nicholls RD. Genomic imprinting: potential function and mechanisms revealed by the Prader-Willi and Angelman syndromes. Molecular human reproduction. 1997; 3(4):321-32.
24. Suzanne B. Cassidy, Stuart Schwartz, Jennifer L. Miller, Daniel J. Driscoll, Prader-Willi syndrome, Genetics in Medicine, Volume 14, Issue 1, 2012, Pages 10-26, https://doi.org/10.1038/gim.0b013e31822bead0.
25. Tucci V, Isles AR, Kelsey G, Ferguson-Smith AC, Bartolomei MS, Benvenisty N, Bourc’his D, Charalambous M, Dulac C, Feil R, Glaser J. Genomic imprinting and physiological processes in mammals. Cell. 2019; 176(5):952-65.
26. Ledbetter, D.H.; Riccardi, V.M.; Airhart, S.D.; Strobel, R.J.; Keenan, B.S.; Crawford, J.D. Deletions of Chromosome 15 as a Cause of the Prader–Willi Syndrome. N. Engl. J. Med. 1981, 304, 325–329.
27. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. The American Journal of Human Genetics. 2010; 86(5):749-64.
28. Lindgren AC. Somatropin therapy for children with Prader-Willi syndrome: guidelines for use. Treatments in Endocrinology. 2006; 5:223-8.
29. Angulo MA, Castro‐Magana M, Lamerson M, Arguello R, Accacha S, Khan A. Final adult height in children with Prader–Willi syndrome with and without human growth hormone treatment. American journal of medical genetics Part A. 2007; 143(13):1456-61.
30. Höybye C. Five‐years growth hormone (GH) treatment in adults with Prader‐Willi syndrome. Acta Paediatrica. 2007; 96(3):410-3.
31. Stevenson DA, Heinemann J, Angulo M, Butler MG, Loker J, Rupe N, Kendell P, Cassidy SB, Scheimann A. Gastric rupture and necrosis in Prader-Willi syndrome. Journal of pediatric gastroenterology and nutrition. 2007; 45(2):272-4.
32. Carrel AL, Lee PD, Mogul HR. Growth hormone and Prader-Willi syndrome. Management of Prader-Willi syndrome. 2022: 195-216.
33. Miller J, Silverstein J, Shuster J, Driscoll DJ, Wagner M. Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome. The Journal of Clinical Endocrinology & Metabolism. 2006; 91(2):413-7.
34. Brice JA. Behavioral and psychotropic interventions in persons with Prader-Willi syndrome. The Endocrinologist. 2000; 10(4):27S-30S.
35. Dykens E, Shah B. Psychiatric disorders in Prader-Willi syndrome: epidemiology and management. CNS drugs. 2003; 17:167-78.
36. Melmet S, Jameson JL (2013) Disorders of the anteritary and hypothalamus. In : Jameson JL (ed) Harrison’s Endocrinology, 3rd edn. McGraw-Hill, Newyork, pp 16-49
Research & Reviews: A Journal of Pharmacology
| Volume | |
| Received | July 16, 2024 |
| Accepted | August 9, 2024 |
| Published | August 12, 2024 |