Genetics of Angelman Syndrome

Angelman Syndrome affects males, females and all racial/ethnic groups equally. There are estimated to be between 1000 and 5000 cases in the U.S. and Canada. AS has been reported throughout the world among divergent racial groups. In North America, the great majority of known cases seem to be of Caucasian origin. Although the exact incidence of AS is unknown, an estimate of between 1 in 15,000 to 1 in 30,000 seems reasonable.
Today, we know Angelman Syndrome is a genetic disorder caused by abnormal function of the gene UBE3A, located within a small region (q11-q13) on chromosome #15. This region is deleted from the maternally derived chromosome in approximately 80% of individuals with Angelman Syndrome. For the remaining 20%, genetic testing can often identify other abnormalities that disrupt UBE3A function. Some individuals in this latter group, however, still have apparently normal genetic laboratory studies; for these, the diagnosis is based solely upon clinical findings.
A. Consistent (100%) Developmental delay, functionally severe, Speech impairment, none or minimal use of words; receptive and non-verbal communication skills higher than verbal ones, Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs, Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span 
B. Frequent (more than 80%) Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2, Seizures, onset usually before 3 years of age, Abnormal EEG, characteristic pattern with large amplitude slow-spike waves (usually 2-3/s), facilitated by eye closure
C. Associated (20-80%) Flat occiput (back of the head), Occipital groove, Protruding tongue, Tongue thrusting; suck/swallowing disorders, Feeding problems during infancy, Prognathia (projecting jaw), Wide mouth, wide-spaced teeth, Frequent drooling, Excessive chewing/mouthing behaviors, Strabismus, Hypopigmented skin, light hair and eye color (compared to family), seen only in deletion cases, Hyperactive lower limb deep tendon reflexes, Uplifted, flexed arm position especially during ambulation, Increased sensitivity to heat, Sleep disturbance, Attraction to/fascination with water.