Angelman syndrome


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Angelman syndrome


Population genetics

Mendelian genetics and punnett squares

Hardy-Weinberg equilibrium

Inheritance patterns

Independent assortment of genes and linkage

Evolution and natural selection

Genetic disorders

Down syndrome (Trisomy 21)

Edwards syndrome (Trisomy 18)

Patau syndrome (Trisomy 13)

Fragile X syndrome

Huntington disease

Myotonic dystrophy

Friedreich ataxia

Turner syndrome

Klinefelter syndrome

Prader-Willi syndrome

Angelman syndrome

Beckwith-Wiedemann syndrome

Cri du chat syndrome

Williams syndrome

Alagille syndrome (NORD)


Polycystic kidney disease

Familial adenomatous polyposis

Familial hypercholesterolemia

Hereditary spherocytosis

Huntington disease

Li-Fraumeni syndrome

Marfan syndrome

Multiple endocrine neoplasia

Myotonic dystrophy


Treacher Collins syndrome

Tuberous sclerosis

von Hippel-Lindau disease


Polycystic kidney disease

Cystic fibrosis

Friedreich ataxia

Gaucher disease (NORD)

Glycogen storage disease type I

Glycogen storage disease type II (NORD)

Glycogen storage disease type III

Glycogen storage disease type IV

Glycogen storage disease type V


Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)

Krabbe disease


Niemann-Pick disease types A and B (NORD)

Niemann-Pick disease type C

Primary ciliary dyskinesia

Phenylketonuria (NORD)

Sickle cell disease (NORD)

Tay-Sachs disease (NORD)



Wilson disease

Fragile X syndrome

Alport syndrome

X-linked agammaglobulinemia

Fabry disease (NORD)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency


Mucopolysaccharide storage disease type 2 (Hunter syndrome) (NORD)

Lesch-Nyhan syndrome

Muscular dystrophy

Ornithine transcarbamylase deficiency

Wiskott-Aldrich syndrome

Mitochondrial myopathy

Autosomal trisomies: Pathology review

Muscular dystrophies and mitochondrial myopathies: Pathology review

Miscellaneous genetic disorders: Pathology review


Angelman syndrome


0 / 8 complete

USMLE® Step 1 questions

0 / 2 complete

High Yield Notes

4 pages


Angelman syndrome

of complete


USMLE® Step 1 style questions USMLE

of complete

A 4-year-old girl with severe intellectual disability is brought to the physician for follow-up. The patient is nonverbal, and she did not begin walking until the age of two. Last year, she was initiated on valproate due to recurrent seizures. During the interview, the physician notices that the patient smiles constantly and laughs most of the time. She claps her hands and laughs hysterically without prompting. Family history is negative for neurological disorders. At the end of the interview, the mother asks the physician about the possibility of having additional children with the same condition. Which of the following is the most appropriate response by the physician?  

External References

First Aid








Angelman syndrome

chromosome association p. 62

imprinting p. 56


Angelman syndrome p. 56

Seizures p. 535

Angelman syndrome p. 56

External Links


Content Reviewers

Rishi Desai, MD, MPH


Tanner Marshall, MS

Angelman syndrome is a genetic disorder that causes intellectual and developmental delay, seizures, frequent laughter, and ataxia, or poor control of voluntary movements.

Now, it happens when a gene on chromosome 15 called UBE3A is not expressed, or transcribed into messenger RNA.

UBE3A stands for ubiquitin-protein ligase E3A, and the protein it codes for is called E6AP or E6-associated protein.

The job of E6AP is to go around tagging, or attaching, a tiny protein called ubiquitin to other proteins, a process called ubiquitination.

Once that happens, the ubiquitinated protein is degraded by the proteasome, a part of the cell’s recycling machinery.

It’s kind of painting an orange U on a tree so that a lumberjack knows to chop it down.

So E6 associated protein has an important job, and it turns out that the region of chromosome 15 around UBE3A is imprinted, imprinting refers to gene expression that’s dependent on the parent of origin of a gene.

This means that either the maternally derived or paternally derived copy of the gene is silenced.

This differs from most genes in the genome, where both the maternal and paternal copies are expressed.

Normally, in the brain, only the maternally derived copy of UBE3A is expressed, while the paternal copy is silenced, unfortunately this process of imprinting leaves the maternal copy of UBE3A vulnerable.

So with the paternal copy of the gene imprinted, and epigenetically silenced, you’ve only got the maternal copy left.

So this means that if anything happens to the maternal copy, the result is Angelman syndrome.

There are a few different types of mutations that can cause Angelman syndrome.

The most common one is a deletion of a couple million base pairs of DNA on the maternal copy of chromosome 15 which includes UBE3A.

Sometimes the deletion overlaps a nearby gene called OCA2, which codes for a pigment that gives color to eye, hair, and skin.

As a result of this, these Angelman syndrome patients can have a light complexion.

A second way is a mutation within the maternal copy of UBE3A, making the protein ineffective.

A third way to get Angelman syndrome is when the entire maternal chromosome 15 is absent and instead there’s an extra copy of the paternal chromosome 15.

This scenario is called paternal uniparental disomy, which means that one parent – the father – contributed two of the same chromosome while the mother contributed none.


Angelman syndrome (AS) is a genetic neurodevelopmental disorder characterized by problems with motor skills, speech, developmental delay, and learning disabilities. People with AS typically have happy dispositions and frequently laugh or smile, even when they are not engaged in activities that would typically elicit such reactions.

Most individuals with AS do not develop fluent speech, have sleep disturbance, and usually have seizures. People with AS typically have a normal life expectancy and have the potential to improve on some self-help skills with proper supportive care.


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