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Prader-Willi syndrome(PWS)

MedGen UID:
46057
Concept ID:
C0032897
Congenital Abnormality
Synonyms: Obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet; Prader Labhart Willi syndrome; PWS
Modes of inheritance:
Sporadic
MedGen UID:
64410
Concept ID:
C0205422
Temporal Concept
SNOMED CT: Prader-Willi syndrome (89392001)
 
Genes: SNORD116-1; PWRN1; SNORD115-1; PWAR1; MAGEL2; NPAP1; MKRN3-AS1; HERC2; MKRN3; SNRPN; NDN; IPW
Cytogenetic locations: 15q11.2; 15q13.1
OMIM: 176270

Disease characteristics

Excerpted from the GeneReview: Prader-Willi Syndrome
Prader-Willi (PWS) syndrome is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless eating is externally controlled). Motor milestones and language development are delayed. All individuals have some degree of cognitive impairment. A distinctive behavioral phenotype (with temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive characteristics) is common. Hypogonadism is present in both males and females and manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature is common; characteristic facial features, strabismus, and scoliosis are often present, and non-insulin-dependent diabetes mellitus often occurs in obese individuals. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Daniel J Driscoll  |  Jennifer L Miller  |  Stuart Schwartz, et. al.   view full author information

Additional descriptions

From OMIM
Prader-Willi syndrome is characterized by diminished fetal activity, obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet. It can be considered to be an autosomal dominant disorder and is caused by deletion or disruption of a gene or several genes on the proximal long arm of the paternal chromosome 15 or maternal uniparental disomy 15, because the gene(s) on the maternal chromosome(s) 15 are virtually inactive through imprinting. Horsthemke and Wagstaff (2008) provided a detailed review of the mechanisms of imprinting of the Prader-Willi/Angelman syndrome (105830) region. See also the chromosome 15q11-q13 duplication syndrome (608636), which shows overlapping clinical features.  http://www.omim.org/entry/176270
From GHR
Prader-Willi syndrome is a complex genetic condition that affects many parts of the body. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, affected individuals develop an insatiable appetite, which leads to chronic overeating (hyperphagia) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes mellitus (the most common form of diabetes). People with Prader-Willi syndrome typically have mild to moderate intellectual impairment and learning disabilities. Behavioral problems are common, including temper outbursts, stubbornness, and compulsive behavior such as picking at the skin. Sleep abnormalities can also occur. Additional features of this condition include distinctive facial features such as a narrow forehead, almond-shaped eyes, and a triangular mouth; short stature; and small hands and feet. Some people with Prader-Willi syndrome have unusually fair skin and light-colored hair. Both affected males and affected females have underdeveloped genitals. Puberty is delayed or incomplete, and most affected individuals are unable to have children (infertile).  http://ghr.nlm.nih.gov/condition/prader-willi-syndrome

Clinical features

Cryptorchidism
MedGen UID:
504309
Concept ID:
CN000029
Finding
Absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the testis.
Hypogonadotrophic hypogonadism
MedGen UID:
504316
Concept ID:
CN000044
Finding
Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones: follicle stimulating hormone (FSH) and luteinizing hormone (LH).
Micropenis
MedGen UID:
504321
Concept ID:
CN000054
Finding
Abnormally small `penis` (FMA:9707). At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Clitoral hypoplasia
MedGen UID:
500882
Concept ID:
CN000060
Finding
Developmental hypoplasia of the `clitoris` (FMA:9909).
Oligomenorrhea
MedGen UID:
504640
Concept ID:
CN000822
Finding
Infrequent periods (less than 6 per year).
Thin upper lip vermilion
MedGen UID:
507078
Concept ID:
CN000212
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Narrow nasal bridge
MedGen UID:
504444
Concept ID:
CN000417
Finding
Decreased width of the bony bridge of the nose.
Upslanted palpebral fissure
MedGen UID:
504509
Concept ID:
CN000546
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Almond-shaped palpebral fissure
MedGen UID:
428753
Concept ID:
CN006914
Finding
A shape created by an acute downward arching of the upper eyelid and upward arching of the lower eyelid, toward the medial canthus, which gives the outline of the palpebral fissures the configuration of an almond. Thus, the maximum distance between the fissures is offset from, and medial to, the center point.
Hypermetropia
MedGen UID:
504484
Concept ID:
CN000506
Finding
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Myopia
MedGen UID:
504487
Concept ID:
CN000511
Finding
An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry.
Esotropia
MedGen UID:
504499
Concept ID:
CN000530
Finding
A form of strabismus with one or both eyes turned inward ('crossed').
Psychosis
MedGen UID:
504566
Concept ID:
CN000666
Finding
A condition characterized by changes of personality and thought patterns often accompanied by hallucinations and delusional beliefs.
Autism
MedGen UID:
504569
Concept ID:
CN000674
Finding
Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV).
Delayed speech and language development
MedGen UID:
504583
Concept ID:
CN000706
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Motor delay
MedGen UID:
504779
Concept ID:
CN001164
Finding
A type of `Developmental delay` (HP:0001263) characterized by a delay in acquiring motor skills.
Specific learning disability
MedGen UID:
504802
Concept ID:
CN001216
Finding
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Ventriculomegaly
MedGen UID:
505112
Concept ID:
CN001919
Finding
An increase in size of the ventricular system of the brain.
Attention deficit hyperactivity disorder
MedGen UID:
506017
Concept ID:
CN006126
Finding
Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient.
Sleep apnea
MedGen UID:
506376
Concept ID:
CN009366
Finding
An intermittent cessation of airflow at the mouth and nose during sleep. Apneas of at least 10 seconds are considered important, but persons with sleep apnea may have apneas of 20 seconds to up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep.
Hyperinsulinemia
MedGen UID:
43779
Concept ID:
C0020459
Disease or Syndrome
A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.
Precocious puberty
MedGen UID:
18752
Concept ID:
C0034013
Disease or Syndrome
Development of SEXUAL MATURATION in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of PUBERTY in the population. This early maturation of the hypothalamic-pituitary-gonadal axis results in sexual precocity, elevated serum levels of GONADOTROPINS and GONADAL STEROID HORMONES such as ESTRADIOL and TESTOSTERONE.
Hypogonadotrophic hypogonadism
MedGen UID:
504316
Concept ID:
CN000044
Finding
Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones: follicle stimulating hormone (FSH) and luteinizing hormone (LH).
Growth hormone deficiency
MedGen UID:
428231
Concept ID:
CN000771
Finding
Insufficient production of growth hormone, which is produced by the anterior pituitary gland. Growth hormone is a major participant in control of growth and metabolism.
Oligomenorrhea
MedGen UID:
504640
Concept ID:
CN000822
Finding
Infrequent periods (less than 6 per year).
Type II diabetes mellitus
MedGen UID:
505874
Concept ID:
CN005268
Finding
A type of diabetes mellitus initially characterized by insulin resistance and hyperinsulinemia and subsequently by glucose interolerance and hyperglycemia.
Hip dysplasia
MedGen UID:
504822
Concept ID:
CN001267
Finding
The presence of `developmental dysplasia` (MPATH:64) of the `hip` (FMA:24964).
Scoliosis
MedGen UID:
427922
Concept ID:
CN002409
Finding
The presence of an abnormal lateral curvature of the spine.
Short palm
MedGen UID:
425240
Concept ID:
CN003783
Finding
Short `palm`(FMA:24920).
Cutaneous photosensitivity
MedGen UID:
428240
Concept ID:
CN000929
Finding
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Hypopigmentation of the skin
MedGen UID:
446388
Concept ID:
CN000946
Finding
A reduction of skin color related to a decrease in melanin production and deposition.
Nasal speech
MedGen UID:
504873
Concept ID:
CN001466
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech, associated with incomplete or weak closure of the velum.
Hyperinsulinemia
MedGen UID:
43779
Concept ID:
C0020459
Disease or Syndrome
A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.
Type II diabetes mellitus
MedGen UID:
505874
Concept ID:
CN005268
Finding
A type of diabetes mellitus initially characterized by insulin resistance and hyperinsulinemia and subsequently by glucose interolerance and hyperglycemia.
Hypoventilation
MedGen UID:
505358
Concept ID:
CN002525
Finding
A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide).
Sleep apnea
MedGen UID:
506376
Concept ID:
CN009366
Finding
An intermittent cessation of airflow at the mouth and nose during sleep. Apneas of at least 10 seconds are considered important, but persons with sleep apnea may have apneas of 20 seconds to up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep.

Professional guidelines

PubMed

August GP, Caprio S, Fennoy I, Freemark M, Kaufman FR, Lustig RH, Silverstein JH, Speiser PW, Styne DM, Montori VM; Endocrine Society
J Clin Endocrinol Metab 2008 Dec;93(12):4576-99. Epub 2008 Sep 9 doi: 10.1210/jc.2007-2458. [Epub ahead of print] PMID: 18782869
Shaffer LG, Agan N, Goldberg JD, Ledbetter DH, Longshore JW, Cassidy SB
Genet Med 2001 May-Jun;3(3):206-11. doi: 10.109700125817-200105000-00011. PMID: 11388763Free PMC Article

Recent clinical studies

Etiology

Tuysuz B, Kartal N, Erener-Ercan T, Guclu-Geyik F, Vural M, Perk Y, Erçal D, Erginel-Unaltuna N
J Pediatr 2014 May;164(5):1064-7. Epub 2014 Feb 25 doi: 10.1016/j.jpeds.2014.01.039. [Epub ahead of print] PMID: 24582009
Nordstrøm M, Hansen BH, Paus B, Kolset SO
Res Dev Disabil 2013 Dec;34(12):4395-403. Epub 2013 Oct 18 doi: 10.1016/j.ridd.2013.09.021. [Epub ahead of print] PMID: 24139709
Marostica E, Grugni G, De Nicolao G, Marazzi N, Crinò A, Cappa M, Sartorio A
Growth Horm IGF Res 2013 Dec;23(6):261-6. Epub 2013 Sep 19 doi: 10.1016/j.ghir.2013.09.004. [Epub ahead of print] PMID: 24090687
Scheermeyer E, Hughes I, Harris M, Ambler G, Crock P, Verge CF, Craig ME, Bergman P, Werther G, van Driel M, Davies PS, Choong CS
J Paediatr Child Health 2013 Dec;49(12):1045-51. Epub 2013 Jun 19 doi: 10.1111/jpc.12294. [Epub ahead of print] PMID: 23781979
Grugni G, Crinò A, Bedogni G, Cappa M, Sartorio A, Corrias A, Di Candia S, Gargantini L, Iughetti L, Pagano C, Ragusa L, Salvatoni A, Spera S, Vettor R, Chiumello G, Brambilla P
Nutr Metab Cardiovasc Dis 2013 Nov;23(11):1134-40. Epub 2012 Dec 7 doi: 10.1016/j.numecd.2012.11.006. [Epub ahead of print] PMID: 23220075

Diagnosis

Lin D, Wang Q, Ran H, Liu K, Wang Y, Wang J, Liu Y, Chen R, Sun Y, Liu R, Ding F
Endocrinology 2014 Jul;155(7):2355-62. Epub 2014 Apr 15 doi: 10.1210/en.2013-2083. [Epub ahead of print] PMID: 24735326
Tuysuz B, Kartal N, Erener-Ercan T, Guclu-Geyik F, Vural M, Perk Y, Erçal D, Erginel-Unaltuna N
J Pediatr 2014 May;164(5):1064-7. Epub 2014 Feb 25 doi: 10.1016/j.jpeds.2014.01.039. [Epub ahead of print] PMID: 24582009
Miller JL, Angulo M
Am J Med Genet A 2014 Feb;164A(2):421-4. Epub 2013 Dec 5 doi: 10.1002/ajmg.a.36306. [Epub ahead of print] PMID: 24311388
Marostica E, Grugni G, De Nicolao G, Marazzi N, Crinò A, Cappa M, Sartorio A
Growth Horm IGF Res 2013 Dec;23(6):261-6. Epub 2013 Sep 19 doi: 10.1016/j.ghir.2013.09.004. [Epub ahead of print] PMID: 24090687
Scheermeyer E, Hughes I, Harris M, Ambler G, Crock P, Verge CF, Craig ME, Bergman P, Werther G, van Driel M, Davies PS, Choong CS
J Paediatr Child Health 2013 Dec;49(12):1045-51. Epub 2013 Jun 19 doi: 10.1111/jpc.12294. [Epub ahead of print] PMID: 23781979

Therapy

Lafortuna CL, Minocci A, Capodaglio P, Gondoni LA, Sartorio A, Vismara L, Rizzo G, Grugni G
J Clin Endocrinol Metab 2014 May;99(5):1816-24. Epub 2014 Jan 28 doi: 10.1210/jc.2013-3607. [Epub ahead of print] PMID: 24471571
Miller JL, Angulo M
Am J Med Genet A 2014 Feb;164A(2):421-4. Epub 2013 Dec 5 doi: 10.1002/ajmg.a.36306. [Epub ahead of print] PMID: 24311388
Bridges N
Arch Dis Child 2014 Feb;99(2):166-70. Epub 2013 Oct 25 doi: 10.1136/archdischild-2013-303760. [Epub ahead of print] PMID: 24162007
Marostica E, Grugni G, De Nicolao G, Marazzi N, Crinò A, Cappa M, Sartorio A
Growth Horm IGF Res 2013 Dec;23(6):261-6. Epub 2013 Sep 19 doi: 10.1016/j.ghir.2013.09.004. [Epub ahead of print] PMID: 24090687
Scheermeyer E, Hughes I, Harris M, Ambler G, Crock P, Verge CF, Craig ME, Bergman P, Werther G, van Driel M, Davies PS, Choong CS
J Paediatr Child Health 2013 Dec;49(12):1045-51. Epub 2013 Jun 19 doi: 10.1111/jpc.12294. [Epub ahead of print] PMID: 23781979

Prognosis

Marostica E, Grugni G, De Nicolao G, Marazzi N, Crinò A, Cappa M, Sartorio A
Growth Horm IGF Res 2013 Dec;23(6):261-6. Epub 2013 Sep 19 doi: 10.1016/j.ghir.2013.09.004. [Epub ahead of print] PMID: 24090687
Bakker NE, Kuppens RJ, Siemensma EP, Tummers-de Lind van Wijngaarden RF, Festen DA, Bindels-de Heus GC, Bocca G, Haring DA, Hoorweg-Nijman JJ, Houdijk EC, Jira PE, Lunshof L, Odink RJ, Oostdijk W, Rotteveel J, Schroor EJ, Van Alfen AA, Van Leeuwen M, Van Pinxteren-Nagler E, Van Wieringen H, Vreuls RC, Zwaveling-Soonawala N, de Ridder MA, Hokken-Koelega AC
J Clin Endocrinol Metab 2013 Oct;98(10):4013-22. Epub 2013 Sep 3 doi: 10.1210/jc.2013-2012. [Epub ahead of print] PMID: 24001750
Hauber M, Stratmann B, Hoedebeck-Stuntebeck N, Tschoepe D
Metab Syndr Relat Disord 2013 Dec;11(6):392-6. Epub 2013 Jul 20 doi: 10.1089/met.2012.0178. [Epub ahead of print] PMID: 23869419
Jabbar A, Khan JN, Singh A, McCann GP
BMJ Case Rep 2013 May 22;2013 doi: 10.1136/bcr-2013-008692. PMID: 23704427
Grugni G, Beccaria L, Corrias A, Crinò A, Cappa M, De Medici C, Di Candia S, Gargantini L, Ragusa L, Salvatoni A, Sartorio A, Spera S, Andrulli S, Chiumello G, Mussa A; Genetic Obesity Study Group of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED)
Clin Endocrinol (Oxf) 2013 Sep;79(3):371-8. Epub 2013 May 11 doi: 10.1111/cen.12150. [Epub ahead of print] PMID: 23311724

Clinical prediction guides

Tuysuz B, Kartal N, Erener-Ercan T, Guclu-Geyik F, Vural M, Perk Y, Erçal D, Erginel-Unaltuna N
J Pediatr 2014 May;164(5):1064-7. Epub 2014 Feb 25 doi: 10.1016/j.jpeds.2014.01.039. [Epub ahead of print] PMID: 24582009
Nordstrøm M, Hansen BH, Paus B, Kolset SO
Res Dev Disabil 2013 Dec;34(12):4395-403. Epub 2013 Oct 18 doi: 10.1016/j.ridd.2013.09.021. [Epub ahead of print] PMID: 24139709
Marostica E, Grugni G, De Nicolao G, Marazzi N, Crinò A, Cappa M, Sartorio A
Growth Horm IGF Res 2013 Dec;23(6):261-6. Epub 2013 Sep 19 doi: 10.1016/j.ghir.2013.09.004. [Epub ahead of print] PMID: 24090687
Scheermeyer E, Hughes I, Harris M, Ambler G, Crock P, Verge CF, Craig ME, Bergman P, Werther G, van Driel M, Davies PS, Choong CS
J Paediatr Child Health 2013 Dec;49(12):1045-51. Epub 2013 Jun 19 doi: 10.1111/jpc.12294. [Epub ahead of print] PMID: 23781979
Pignatti R, Mori I, Bertella L, Grugni G, Giardino D, Molinari E
J Appl Res Intellect Disabil 2013 Nov;26(6):568-77. Epub 2013 Apr 24 doi: 10.1111/jar.12047. [Epub ahead of print] PMID: 23613474

Recent systematic reviews

Yang L, Zhan GD, Ding JJ, Wang HJ, Ma D, Huang GY, Zhou WH
PLoS One 2013;8(8):e72640. Epub 2013 Aug 14 doi: 10.1371/journal.pone.0072640. PMID: 23967326Free PMC Article
Deal CL, Tony M, Höybye C, Allen DB, Tauber M, Christiansen JS; 2011 Growth Hormone in Prader-Willi Syndrome Clinical Care Guidelines Workshop Participants
J Clin Endocrinol Metab 2013 Jun;98(6):E1072-87. Epub 2013 Mar 29 doi: 10.1210/jc.2012-3888. [Epub ahead of print] PMID: 23543664Free PMC Article
Bervini S, Herzog H
Front Neuroendocrinol 2013 Apr;34(2):107-19. Epub 2013 Feb 4 doi: 10.1016/j.yfrne.2013.01.002. [Epub ahead of print] PMID: 23391702
Reus L, van Vlimmeren LA, Staal JB, Otten BJ, Nijhuis-van der Sanden MW
Neurosci Biobehav Rev 2012 Sep;36(8):1817-38. Epub 2012 May 28 doi: 10.1016/j.neubiorev.2012.05.005. [Epub ahead of print] PMID: 22652271
Sanchez-Ortiga R, Klibanski A, Tritos NA
Clin Endocrinol (Oxf) 2012 Jul;77(1):86-93. doi: 10.1111/j.1365-2265.2011.04303.x. PMID: 22117629

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