Rare Nephrology News

Disease Profile

Angelman 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

Infancy

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ICD-10

Q93.5

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.

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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)

AS; Happy puppet syndrome (formerly)

Categories

Congenital and Genetic Diseases; RDCRN

Summary

Angelman syndrome is a genetic disorder that primarily affects the nervous system. Characteristic features of this condition include developmental delay, intellectual disability, severe speech impairment, problems with movement and balance (ataxia), epilepsy, and a small head size. Individuals with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. Many of the characteristic features of Angelman syndrome result from the loss of function of a gene called UBE3A. Most cases of Angelman syndrome are not inherited, although in rare cases a genetic change responsible for Angelman syndrome can be inherited from a parent.[1] Treatment is aimed at addressing each individual's symptoms and may include antiepileptics for seizures; physical, occupational, and speech therapy; and special education services.[2]

Symptoms

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
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal

[ more ]

0001344
Ataxia
0001251
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

0000708
Blue irides
Blue eyes
0000635
Brachycephaly
Short and broad skull
0000248
Broad-based gait
Wide based walk
0002136
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Clumsiness
0002312
EEG abnormality
0002353
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation

[ more ]

0006887
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

0000158
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

0000303
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Muscular hypotonia
Low or weak muscle tone
0001252
Seizure
0001250
30%-79% of people have these symptoms
Hyperreflexia
Increased reflexes
0001347
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Sporadic
No previous family history
0003745
Wide mouth
Broad mouth
Large mouth

[ more ]

0000154
Widely spaced teeth
Wide-spaced teeth
Widely-spaced teeth

[ more ]

0000687
5%-29% of people have these symptoms
Inguinal hernia
0000023
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Constipation
0002019
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

0000490
Drooling
Dribbling
0002307
Exotropia
Outward facing eye ball
0000577
Fair hair
Blond hair
Fair hair color
Flaxen hair color
Light colored hair
Sandy hair color
Straw colored hair
Towhead (hair color)

[ more ]

0002286
Feeding difficulties in infancy
0008872
Flat occiput
0005469
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Hyperactivity
More active than typical
0000752
Hypopigmentation of the skin
Patchy lightened skin
0001010
Limb tremor
Involuntary shaking of limb
0200085
Motor delay
0001270
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Obesity
Having too much body fat
0001513
Paroxysmal bursts of laughter
0000749
Progressive gait ataxia
0007240
Protruding tongue
Prominent tongue
Tongue sticking out of mouth

[ more ]

0010808
Scoliosis
0002650
Sleep-wake cycle disturbance
0006979

Cause

Angelman syndrome is caused by a loss of function of a gene called UBE3A on chromosome 15. The exact mechanism that causes this loss of function is complex. People normally inherit one copy of the UBE3A gene from each parent. Both copies of this gene are turned on (active) in many of the body's tissues. In certain areas of the brain, however, only the copy inherited from a person's mother is active. This parent-specific gene activation is known as genomic imprinting. If the maternal copy of the UBE3A gene is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the gene in some parts of the brain.[1]

Several different genetic mechanisms can inactivate or delete the maternal copy of the UBE3A gene. Most cases of Angelman syndrome occur when a segment of the maternal chromosome 15 containing this gene is deleted. In other cases, Angelman syndrome is caused by a mutation in the maternal copy of the UBE3A gene.[1]

In a small percentage of cases, a person with Angelman syndrome inherits two copies of chromosome 15 from his or her father, instead of one copy from each parent. This is called paternal uniparental disomy. Rarely, Angelman syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect in the region of DNA that controls activation of the UBE3A gene. These genetic changes can abnormally turn off (inactivate) UBE3A or other genes on the maternal copy of chromosome 15.[1]

The cause of Angelman syndrome is unknown in 10 to 15 percent of affected individuals. Changes involving other genes or chromosomes may be responsible for the condition in these individuals.[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

    Management Guidelines

    • 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.

      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.
          • 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 Angelman syndrome. Click on the link to view a sample search on this topic.

            References

            1. Angelman syndrome. Genetics Home Reference. May 2015; https://ghr.nlm.nih.gov/condition=angelmansyndrome.
            2. Dagli AI, Mueller J, Williams CA. Angelman Syndrome. GeneReviews. May 14, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1144/.

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