Courtagen Life Sciences Blog

Disease Spotlight: Angelman Syndrome

Posted by Sarah Klemm, MS, CGC on Apr 12, 2017 2:23:00 PM

Angelman Syndrome-734793-edited.jpg

Photo Source: Angelman Syndrome Foundation

Angelman syndrome is a genetic condition that causes developmental and intellectual disabilities. Common features seen in Angelman syndrome are seizures, ataxia, unique facial features, small head size (microcephaly), and behavioral differences.

The behavioral features of Angelman syndrome include an excitable happy demeanor with frequent laughing and smiling. Approximately 1/12,000 to 1/24,000 people are affected with Angelman Syndrome, and the disorder is not more common in any population or gender.

Diagnosing Angelman Syndrome

Angelman syndrome can be diagnosed through clinical examination using published consensus criteria and/or by molecular genetic testing that detects loss of expression of the maternal copy of the UBE3A gene. (PMIDs: 16470747, 22670133, 23498559, 24876791).

Genetics of Angelman Syndrome

Angelman Syndrome is an autosomal dominant genetic disease. Autosomal dominance is a term used to describe the inheritance pattern for a genetic disorder. "Autosomal" means that the gene in question, in this case UBE3A, is located on one of the non-sex chromosomes. "Dominant" means that there only needs to be one copy of the disease-associated mutation in order to cause disease.

Angelman syndrome is caused by loss of the expression of the copy of the UBE3A gene inherited from the patient’s mother. This means that the protein produced from the maternal copy of the UBE3A gene is absent or has impaired function. In Angelman syndrome, the genetic changes are only related to the maternally inherited copy of UBE3A.

Nearly two out of three cases (~68%) of Angelman Syndrome are caused by a deletion of the UBE3A gene. Other causes include:

  • Mutations in UBE3A (~11%)
  • Uniparental disomy, when two copies of a gene come from the father (~7%)
  • Imprinting center defects (~3%).
    • Imprinting center defects cause altered protein expression by not allowing the body to add the right methylation pattern to the UBE3A. It is the methylation pattern of UBE3A that tells the body which copy of the gene to use, the one inherited from the mother or the one inherited from the father.
  • Unidentifiable genetic change.

The chance for a couple to have multiple children with this condition depends on the underlying genetic cause.

The UBE3A gene is covered on several Courtagen Next Generation Sequencing panels including devSEEK® Triome, epiSEEK® Triome, and Microcephaly Spotlight Panel. Use our gene search tool to see the full list of panels that include UBE3A.

Treatment options

The management of Angelman syndrome is symptom based. Common treatments include, early intervention, developmental therapies, and neurologic care.

There are also several contraindications associated with Angelman Syndrome, which are therapies that can cause harm. Vigabatrin and tigabine (anticonvulsants that increase brain GABA levels) are contraindicated in individuals with Angelman syndrome. For unknown reasons, carbamazapine, vigabatrine, and tigabine can also cause development of other seizure types or non-convulsive status epilepticus.

Further Reading and Support

The resources below can be used to learn more about Angelman Syndrome or access support services for families who are affected by the disease.

Topics: Developmental Delay