Is Angelman Syndrome hereditary?

Is Angelman Syndrome Hereditary?

Angelman Syndrome (AS) is a rare genetic disorder that affects the nervous system, causing severe developmental delays, intellectual disabilities, and a unique set of physical characteristics. It was first described by Dr. Harry Angelman in 1965, hence the name.

Causes of Angelman Syndrome:

AS is primarily caused by a genetic mutation or deletion on chromosome 15. There are several different genetic mechanisms that can lead to Angelman Syndrome:

• Deletion: Approximately 70% of individuals with AS have a deletion in the maternally inherited chromosome 15. This means that a small piece of genetic material is missing from the mother's chromosome 15.


• Uniparental Disomy (UPD): In about 2-5% of cases, both copies of chromosome 15 are inherited from the father, with no contribution from the mother. This occurs when the child inherits two copies of chromosome 15 from the father and none from the mother.


• Imprinting Defect: Another 2-5% of individuals with AS have an imprinting defect, where the genes on the maternally inherited chromosome 15 are not properly turned on or off.


• UBE3A Gene Mutation: In approximately 10-15% of cases, individuals have a mutation in the UBE3A gene, which is located on chromosome 15. This gene provides instructions for making a protein that is essential for normal brain development.

Inheritance Patterns:

Angelman Syndrome can be inherited in different ways depending on the underlying genetic mechanism:

• Deletion: When a child has a deletion on chromosome 15, it usually occurs as a random event during the formation of reproductive cells (eggs or sperm) or early in embryonic development. In these cases, the deletion is typically not inherited from either parent and is considered a de novo mutation.


• Uniparental Disomy (UPD): In cases of UPD, the child inherits both copies of chromosome 15 from the father and none from the mother. This can happen when there is an error in the egg or sperm cells, leading to two copies of the father's chromosome 15 being passed on to the child.


• Imprinting Defect: Imprinting defects can occur sporadically and are not usually inherited from either parent. They are caused by errors in the chemical marks that regulate gene expression on the maternally inherited chromosome 15.


• UBE3A Gene Mutation: UBE3A gene mutations can be inherited from an unaffected carrier parent or occur as a spontaneous mutation. In some cases, a parent may carry a mutation in the UBE3A gene but not exhibit any symptoms of Angelman Syndrome.

Genetic Testing and Counseling:

If a child is diagnosed with Angelman Syndrome, genetic testing can help determine the underlying genetic mechanism. This information is crucial for understanding the inheritance pattern and providing appropriate genetic counseling to families.

Genetic counseling is recommended for families affected by Angelman Syndrome, as it can provide information about the risk of recurrence in future pregnancies. The specific risk depends on the underlying genetic cause and whether it was inherited or occurred spontaneously.

Conclusion:

Angelman Syndrome can be caused by different genetic mechanisms, including deletions, uniparental disomy, imprinting defects, and UBE3A gene mutations. While some cases are inherited, others occur spontaneously as de novo mutations. Genetic testing and counseling are essential for understanding the specific genetic cause and providing appropriate guidance to affected families.