Angelman syndrome (AS) is a genetic disorder that affects the nervous system. It is characterized by developmental delay, intellectual disability, severe speech impairment, gait ataxia, tremulousness of the limbs, seizures, microcephaly, and a unique behavior with inordinately happy disposition (frequent laughing, smiling, and excitability). Developmental delays are the first feature of AS to be observed at the age of six to 12 months, however, the other clinical features of the disease appear later in early childhood. Patients mostly have a short attention span. Unusually fair skin and light-coloured hair may be noticed in some patients with AS. The incidence rate of AS is unknown, but some researches have estimated it to be 1:20,000. The disease is diagnosed usually by clinical manifestation as well as EEG findings. Management strategies include physical and psychomotor therapy, speech therapy, psychological and educational approaches, and drugs for treating epilepsy, behavior and sleep disorders.
Usually, Angelman syndrome (AS) is not inherited, but occurs due to random events that happen during the formation of the germ cells or in early fetal development. The disease results from de novo maternal deletion in 15q11.2-q13 region that is known as the Angelman syndrome/Prader-Willi syndrome (AS/PWS) region. Five different mechanisms are known to cause the loss of the maternally contributed AS/PWS region; these are - deletion (70% of the cases), paternal uniparental disomy, imprinting defects, mutation of the ubiquitin-protein ligase (UBE3A) gene, and other unidentified mechanisms. The five mechanisms will result in having similar manifestations of the disease. However, the risk to sibs of a patient with AS depends upon the genetic mechanism that causes the loss of the maternally contributed AS/PWS region. For example, those sibs will be at a higher risk if the disease is caused by mutations in the UBE3A gene, whereas a lower risk will exist in cases with deletion or uniparental disomy. In addition, it has been found that the oculocutaneous albinism, type II (OCA2) gene is associated with AS which is often deleted in cases with AS. This gene encodes a protein that is responsible for the pigmentation of skin, hair, and eyes, thereby, some patients are presenting with light-colored hair and fair skin.