Epidemiology and genetics of Prader-Willi syndrome
- Ann O Scheimann, MD, MBA
Ann O Scheimann, MD, MBA
- Associate Professor of Pediatrics
- Johns Hopkins School of Medicine
- Section Editors
- Mitchell Geffner, MD
Mitchell Geffner, MD
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Keck School of Medicine, University of Southern California
- Melvin B Heyman, MD, MPH
Melvin B Heyman, MD, MPH
- Section Editor — Gastroenterology
- Professor of Pediatrics
- University of California, San Francisco
Prader-Willi syndrome (PWS), also known as Prader-Willi-Labhart syndrome, is the most common syndromic form of obesity and is caused by absence of expression of the paternally active genes in a discrete region on the long arm of chromosome 15, either due to deletions from the paternal chromosome or maternal disomy. The vast majority of cases occur sporadically. In adults and children, the primary clinical features are hyperphagia, usually leading to early-onset obesity, hypogonadism, developmental delay, and characteristic facial features. In infants, the most prominent findings are hypotonia and feeding difficulties.
The epidemiology and genetics of PWS will be reviewed here. The clinical features, diagnosis, and approaches to treatment of this disorder are discussed separately. (See "Clinical features, diagnosis, and treatment of Prader-Willi syndrome".)
In 1887, Langdon-Down described the first girl with probable Prader-Willi syndrome (PWS), manifest by mental impairment, short stature, hypogonadism, and obesity; he termed the condition polysarcia . Seventy years later, Prader and colleagues reported a series of patients with similar phenotypes . In 1981, Ledbetter, et al, identified microdeletions within chromosome 15 as the site for PWS .
Prader-Willi syndrome (PWS) is the most common syndromic form of obesity and affects between 350,000 and 400,000 individuals worldwide. Both sexes are affected equally .
Although prevalence estimates differ among studies, this is likely due to using different methods for case identification, and there is no strong evidence for increased risk in specific countries or gene pools. Within the United States, the rate of prevalence has been reported between 1 in 16,062  to 1 in 25,000 . Outside of the United States, reported prevalence rates for PWS range from 1 per 8,000 in rural Sweden  to 1 per 16,000 in Western Japan , 1:15,830 in Australia , and a birth incidence of 1 per 27,000 in Flanders . Within the United Kingdom, a lower population prevalence of 1 in 52,000 was estimated, with a proposed true prevalence of 1 in 45,000 . In each of these populations, PWS represents a very small fraction of children with obesity, or even severe obesity.
- Down JL. Affections of Childhood and Youth, Churchill Publisher, London 1887. p.172.
- Prader A, Labhart A, Willi H. Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus, und Oligophrenie Nach Myatonieartigem Zustard in Neugeborenenalter. Schweiz Med Wschr 1956; 86:1260.
- Ledbetter DH, Riccardi VM, Airhart SD, et al. Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med 1981; 304:325.
- Butler MG, Hanchett JM, Thompson T. Clinical findings and natural history of Prader-Willi syndrome. In: Management of Prader-willi Syndrome, Butler MG, Lee PDK, Whitman BY (Eds), Springer, New York 2006.
- Burd L, Vesely B, Martsolf J, Kerbeshian J. Prevalence study of Prader-Willi syndrome in North Dakota. Am J Med Genet 1990; 37:97.
- Butler MG. Prader-Willi syndrome: current understanding of cause and diagnosis. Am J Med Genet 1990; 35:319.
- Akefeldt A, Gillberg C, Larsson C. Prader-Willi syndrome in a Swedish rural county: epidemiological aspects. Dev Med Child Neurol 1991; 33:715.
- Ehara H, Ohno K, Takeshita K. Frequency of the Prader-Willi syndrome in the San-in district, Japan. Brain Dev 1995; 17:324.
- Lionti T, Reid SM, White SM, Rowell MM. A population-based profile of 160 Australians with Prader-Willi syndrome: trends in diagnosis, birth prevalence and birth characteristics. Am J Med Genet A 2015; 167A:371.
- Vogels A, Van Den Ende J, Keymolen K, et al. Minimum prevalence, birth incidence and cause of death for Prader-Willi syndrome in Flanders. Eur J Hum Genet 2004; 12:238.
- Whittington JE, Holland AJ, Webb T, et al. Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet 2001; 38:792.
- Tuysuz B, Kartal N, Erener-Ercan T, et al. Prevalence of Prader-Willi syndrome among infants with hypotonia. J Pediatr 2014; 164:1064.
- Hou JW, Wang TR, Chuang SM. An epidemiological and aetiological study of children with intellectual disability in Taiwan. J Intellect Disabil Res 1998; 42 ( Pt 2):137.
- Whittington JE, Butler JV, Holland AJ. Changing rates of genetic subtypes of Prader-Willi syndrome in the UK. Eur J Hum Genet 2007; 15:127.
- Buiting K, Horsthemke B. Molecular genetic findings in Prader-Willi syndrome. In: Management of Prader-Willi syndrome, 3 Ed, Butler MG, Lee PDK, Whitman BY. (Eds), Springer, New York 2006. p.58.
- Driscoll DJ, Miller JL, Schwartz S, and Cassidy SB. Prader-Willi Syndrome (a GeneReviews monograph). Available at: http://www.ncbi.nlm.nih.gov/books/NBK1330/ (Accessed on February 12, 2014).
- Larson FV, Whittington J, Webb T, Holland AJ. A longitudinal follow-up study of people with Prader-Willi syndrome with psychosis and those at increased risk of developing psychosis due to genetic subtype. Psychol Med 2014; 44:2431.
- Hosoki K, Kagami M, Tanaka T, et al. Maternal uniparental disomy 14 syndrome demonstrates prader-willi syndrome-like phenotype. J Pediatr 2009; 155:900.
- Mitter D, Buiting K, von Eggeling F, et al. Is there a higher incidence of maternal uniparental disomy 14 [upd(14)mat]? Detection of 10 new patients by methylation-specific PCR. Am J Med Genet A 2006; 140:2039.
- Buiting, K, Horsthemke, B. Molecular Genetic Findings in Prader-willi Syndrome in Management of Prader-willi Syndrome, Butler MG, Lee PDK, Whitman BY (Eds), Springer, New York 2006. p.63.
- Sahoo T, del Gaudio D, German JR, et al. Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat Genet 2008; 40:719.
- Duker AL, Ballif BC, Bawle EV, et al. Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome. Eur J Hum Genet 2010; 18:1196.
- Schaaf CP, Gonzalez-Garay ML, Xia F, et al. Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat Genet 2013; 45:1405.
- Monaghan KG, Van Dyke DL. Laboratory testing for Prader-Willi syndrome. In: Management of Prader-willi Syndrome, Butler MG, Lee PDK, Whitman BY (Eds), Springer, New York 2006. p.79.