Mathews Adera, MD, Vice President, Neurodevelopment at Ovid Therapeutics discusses some signs and symptoms of Angelman syndrome and the difficulty of diagnosing this rare disorder.

Angelman syndrome is a rare genetic disorder affecting roughly 500,000 people worldwide. Patients with Angelman syndrome generally experience developmental delays, intellectual disabilities, extensive speech impairment, issues with movement and balance, epilepsy, and abnormal sleep-wake. 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, located on chromosome 15. UBE3A gene provides instructions for making a protein called ubiquitin protein ligase E3A. Studies suggest that ubiquitin protein ligase E3A plays a critical role in the normal development and function of the nervous system. Both copies of UBE3A are active in several areas of the body; however, the brain has only one activated copy of the gene, which is inherited by the mother. If this copy of the gene is randomly deleted or mutated, the body cannot call upon the father’s contributed UBE3A in this area of the brain to take its place. When this happens, the signs of Angelman syndrome will emerge. In very rare cases (1%), an infant with Angelman syndrome can inherit both chromosome 15 copies by the father, meaning that the mother’s copy is absent and yielding the same result.

According to the latest research, the problem is most commonly the result of a deleted segment on chromosome 15. The deletion or mutation often occurs during germ cell production or during development of the early embryo. In approximately 10% of patients, the patient has both copies of the gene, and the cause of the disorder cannot be determined. In those patients, scientists believe that a combination of other mutations or chromosomal deletions may occur, which culminate in the same effect.

The prevalence of Angelman syndrome is between 1 in 12,000 and 1 in 20,000 individuals. This means more than 20,000 Americans are affected by the disorder; males and females seem equally affected.

For more information on Angelman syndrome, visit the Angelman Syndrome Learning Center.