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Disease Profile

Prader-Willi syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

PWS; Willi-Prader syndrome; Prader-Labhart-Willi syndrome

Categories

Congenital and Genetic Diseases; RDCRN

Summary

Prader-Willi syndrome (PWS) is a genetic condition that affects many parts of the body. Infants with PWS have severe hypotonia (low muscle tone), feeding difficulties, and slow growth. In later infancy or early childhood, affected children typically begin to eat excessively and become obese. Other signs and symptoms often include short stature, hypogonadism, developmental delays, cognitive impairment, and distinctive behavioral characteristics such as temper tantrums, stubbornness, and obsessive-compulsive tendencies. PWS is caused by missing or non-working genes on chromosome 15. Most cases are not inherited and occur randomly. Rarely, a genetic change responsible for PWS can be inherited. Management of PWS generally depends on the affected person's age and symptoms.[1][2]

Symptoms

In infancy, Prader-Willi syndrome (PWS) is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. In later infancy or early childhood, affected children develop an extreme appetite, which leads to overeating and obesity.[2][1]

Other signs and symptoms of PWS may include:[2][1]

  • mild to moderate intellectual disability
  • sleep abnormalities
  • unusually fair skin
  • underdeveloped genitals
  • delayed or incomplete puberty
  • short stature
  • strabismus
  • scoliosis
  • small hands and feet
  • distinctive facial features such as a narrow forehead, almond-shaped eyes, and a triangular mouth

Behavioral problems are common and often include temper tantrums, stubbornness, and obsessive-compulsive tendencies.[2][1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Central hypotonia
0011398
Cryptorchidism
Undescended testis
Undescended testes

[ more ]

0000028
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech delay
Speech and language difficulties

[ more ]

0000750
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Growth hormone deficiency
0000824
Hypogonadotropic hypogonadism
0000044
Infertility
0000789
Motor delay
0001270
Narrow palm
0004283
Polyphagia
Voracious appetite
0002591
Poor suck
Poor sucking
0002033
Short foot
Short feet
Small feet

[ more ]

0001773
Short palm
0004279
Short stature
Decreased body height
Small stature

[ more ]

0004322
Specific learning disability
0001328
30%-79% of people have these symptoms
Abdominal obesity
Central obesity
0012743
Abnormal facial shape
Unusual facial appearance
0001999
Abnormal rapid eye movement sleep
0002494
Almond-shaped palpebral fissure
Almond shaped eyes
Almond-shaped opening between the eyelids

[ more ]

0007874
Attention deficit hyperactivity disorder
Attention deficit
Childhood attention deficit/hyperactivity disorder
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits

[ more ]

0007018
Brain imaging abnormality
0410263
Central adrenal insufficiency
0011734
Central sleep apnea
0010536
Clitoral hypoplasia
Small clitoris
Underdeveloped clit

[ more ]

0000060
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity

[ more ]

0000992
Decreased circulating gonadotropin level
0030339
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
Decreased muscle mass
0003199
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Diabetes mellitus
0000819
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

0002714
Edema
Fluid retention
Water retention

[ more ]

0000969
Erysipelas
0001055
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Gastroparesis
Delayed gastric emptying
0002578
Hypogonadism
Decreased activity of gonads
0000135
Hypopigmentation of hair
Loss of hair color
0005599
Hypopigmentation of the skin
Patchy lightened skin
0001010
Hypoplastic labia majora
Small labia majora
Underdeveloped vaginal lips

[ more ]

0000059
Hypoplastic labia minora
Underdeveloped inner lips
0000064
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Impaired pain sensation
Decreased pain sensation
0007328
Impaired temperature sensation
Abnormality of temperature sensation
Loss of temperature sensation

[ more ]

0010829
Increased susceptibility to fractures
Abnormal susceptibility to fractures
Bone fragility
Frequent broken bones
Increased bone fragility
Increased tendency to fractures

[ more ]

0002659
Intellectual disability, borderline
Mental retardation, borderline
0006889
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Kyphosis
Hunched back
Round back

[ more ]

0002808
Micropenis
Short penis
Small penis

[ more ]

0000054
Narrow forehead
Decreased width of the forehead

Cause

Prader-Willi syndrome (PWS) is caused by the loss of active genes in a specific region of chromosome 15. People normally inherit one copy of chromosome 15 from each parent. Some genes on chromosome 15 are only active (or "expressed") on the copy that is inherited from a person's father (the paternal copy). When genes are only active if inherited from a specific parent, it is called genomic imprinting.

About 70% of cases of PWS occur when a person is missing specific genes on the long arm of the paternal copy of chromosome 15. This is called a deletion. While there are copies of these same genes on the maternal copy of chromosome 15, the maternal copies of these genes are not expressed.

In about 25% of cases, PWS is due to a person inheriting only 2 maternal copies of chromosome 15, instead of one copy from each parent. This is called maternal uniparental disomy.

Rarely (in about 2% of cases), PWS is caused by a rearrangement of chromosome material called a translocation, or by a change (mutation) or other defect that abnormally inactivates genes on the paternal chromosome 15.[1]

Each of these genetic changes result in a loss of gene function on part of chromosome 15, likely causing the characteristic features of PWS.[1]

Diagnosis

There are clinical diagnostic criteria for Prader-Willi syndrome (PWS) that were developed in the past that continue to be useful. These criteria can be viewed on the National Institute of Health's NICHD Web site.

However, the current mainstay of a diagnosis when PWS is suspected is a form of genetic testing called DNA methylation testing. This testing can detect abnormal, parent-specific imprinting on the region of chromosome 15 that is responsible for PWS. It determines whether the region is maternally inherited only (i.e., the paternally contributed region is absent) and confirms a diagnosis in more than 99% of affected people. DNA methylation testing is especially important in people who have non-classic features, or are too young to show enough features to make the diagnosis based on signs and symptoms alone.[2][3]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    A multidisciplinary team approach is ideal for the treatment of people with Prader-Willi syndrome (PWS). Early diagnosis, early multidisciplinary care, and growth hormone treatment have greatly improved the quality of life of many affected children. In general, management of this condition depends on the affected person's age and symptoms.[2][3]

    When a diagnosis of PWS is made, several evaluations are needed to assess the extent of the condition. For example, newborns should be assessed for sucking problems; infants should be assessed for development; and young children should have a vision exam. All males should be evaluated for the presence of cryptorchidism. Other associated conditions for which evaluations may be recommended include hypothyroidism, scoliosis, behavioral problems, psychosis, and respiratory problems and sleep issues.[2][3]

    In infants, special feeding techniques may be needed. Young children often need early intervention, including physical therapy for muscle strength and reaching physical milestones, and speech therapy for language issues. Cryptorchidism may resolve on its own but usually requires hormonal and/or surgical treatment. When excessive eating begins and weight percentiles increase, affected children should be on a program of a well-balanced diet, exercise, and close supervision with food. A consultation with a dietitian is recommended. Behavioral problems may be addressed with special behavioral management programs. Serotonin uptake inhibitors have helped many affected teenagers and adults, particularly those with obsessive-compulsive symptoms.[2][3]

    Growth hormone treatment can normalize height, increase lean body mass, increase mobility, and decrease fat mass. Controlled trials of growth hormone therapies have shown significant benefit from infancy through adulthood. Benefits may include an increase in language and cognitive skills, and better motor performance. Sex hormone replacement helps to produce secondary sex characteristics (those that develop during puberty) but is somewhat controversial due to possible behavior problems in males, risk of stroke, and hygiene concerns related to menstruation in females.[2][3]

    Clinical trials investigating potential treatment options for people with PWS are ongoing. ClinicalTrials.gov provides patients, family members, and members of the public with current information on clinical research studies for PWS. Use each study's contact information to learn more.

    Management Guidelines

    • The Foundation for Prader-Willi Research provides an overview of diagnosis and treatment for Prader-Willi syndrome.
    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      FDA-Approved Treatments

      The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

      • Somatropin (r-DNA) for injection(Brand name: Genotropin) Manufactured by Pfizer, Inc.
        FDA-approved indication: Long-term treatment of pediatric patients who have growth failure due to Prader-Willi syndrome (PWS). (Genotropin is not appropriated for all children with PWS, so please talk to your doctor.)
        National Library of Medicine Drug Information Portal

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Prader-Willi syndrome. Click on the link to view a sample search on this topic.

            References

            1. Prader-Willi syndrome. Genetics Home Reference. June 2014; https://ghr.nlm.nih.gov/condition/prader-willi-syndrome#.
            2. Driscoll DJ, Miller JL, Schwartz S, and Cassidy SB. Prader-Willi Syndrome. GeneReviews. February 4 2016; https://www.ncbi.nlm.nih.gov/books/NBK1330/.
            3. Prader-Willi syndrome Diagnosis and Treatments. Foundation for Prader-Willi Research. https://www.fpwr.org/prader-willi-syndrome-diagnosis-treatments/. Accessed 7/7/2016.
            4. Ann Scheimann. Prader-Willi Syndrome. Medscape. March 18, 2014; https://emedicine.medscape.com/article/947954-overview. Accessed 1/6/2015.
            5. FAQ. Prader-Willi Syndrome Association. 2015; https://www.pwsausa.org/about-pws/faq. Accessed 9/23/2015.

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