Angelman Syndrome By Jeaneane P. Kozlowski Presented July 1, 2003 Temple University- Ambler College

About the Little Angels Angelman Syndrome (AS) came as a result of the work and research of Dr. Harry Angelman in AS is a genetic disorder caused by abnormal function of the gene UBE3A, located within a small region on chromosome #15. This region is deleted from the maternally derived chromosome in approximately 80% of individuals with Angelman Syndrome. The remaining 20%, genetic testing can often identify other abnormalities that disrupt UBE3A function. Some individuals have apparently normal genetic laboratory studies; for these, the diagnosis is based solely upon clinical findings.

Developmental and Physical Features AS usually not recognized at birth or in infancy; developmental problems are nonspecific during this time. Parents may first suspect the diagnosis after reading about AS or meeting a child with the condition. Common age of diagnosis is between three and seven years when characteristic behaviors and features become most evident. All of the features do not need to be present for the diagnosis to be made, and the diagnosis is often first suspected when the typical behaviors are recognized.

Consensus Criteria for Clinical Features in Angelman Syndrome Consistent Features- 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 Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor Easily excitable personality, often with hand flapping movements; Hypermotoric behavior Short attention span

Frequent Features Associated Features (more than 80%) ( %) Delayed, disproportionate growth in head circumference (absolute or relative) by age 2 Seizures, onset usually < 3 years of age Abnormal EEG Extremely light skin and eyes Tongue thrusting; suck/swallowing disorders Feeding problems during infancy Increased sensitivity to heat Wide mouth, wide-spaced teeth Sleep disturbance Frequent drooling, protruding tongue Attraction to/fascination with water Excessive chewing/mouthing behaviors Flat back of head

Touched by an Angel…a Child with AS This is “Angel”. When this picture was taken “Angel” was 3 years old. She is just beginning to walk with assistance. The following are pictures that show her physical development as compared to a developmentally normal boy 15 months younger than her.

“Angel” and Logan In these picture “Angel” is 18 mo. Logan is 3 1/2 mo. Notice Her tiny frame and extremely small head circumference.

A Happy Puppet This picture shows the “puppet-like” physical feature of the syndrome. Children with AS are almost always smiling and often laugh uncontrollably at inappropriate times.

Classes of Angelman Syndrome Large typical deletion 70% Hypopigmentation is common UBE3A mutation5-7%Possibility of normal carrier mother Paternal uniparental disomy 2-3% Inheritance of both 15s from father Imprinting defect 3-5% Some have IC deletion, some do not Other chromosome abnormalities 2% Unusual chromosome rearrangements Unknown15% All diagnostic tests negative (FISH, methylation, UBE3A mutation analysis)

Speech and Language Development Some AS children seem to have enough comprehension to be able to speak, but in even the highest functioning, conversational speech does not develop. Children with AS caused by uniparental disomy or extremely small deletions may have higher verbal and cognitive skills; at times use of words may occur, with awkward pronunciation. Babies and young infants cry less often and have decreased cooing and babbling. A single apparent word, such as "mama," may develop around months but used infrequently and indiscriminately without symbolic meaning. 2-3 years of age, clear that speech is delayed may not be evident how little the AS child is verbally communicating; crying and other vocal outbursts may also be reduced.

By 3 years of age, higher functioning AS children are initiating some type of non-verbal language. Some point to body parts and indicate some of their needs by use of simple gestures. Much better at following and understanding commands. Others, especially those with severe seizures or extreme hyperactivity cannot be attentive enough to achieve the first stages of communication, such as establishing sustained eye contact. The nonverbal language skills of AS children vary greatly; with the most advanced ones able to learn some sign language and to use such aids as picture-based communication boards.

An Angel at Play Even though “Angel” can not verbally communicate, it does not stop her from having fun. Children with AS learn nonverbal forms of communication. Body language is extremely important. “Angel” (3 yrs.) playing rough with Logan (22 mo.)

Education For Angels The severe developmental delay in AS mandates that a full range of early training and enrichment programs be made available. Speech and communication therapy essential & should focus on nonverbal methods of communication. Augmentative communication aids(picture cards or communication boards) used at the earliest appropriate time. Extremely active AS children will require special provisions in the classroom; teacher aides or assistants may be needed to integrate the child into the classroom. Structured classroom setting, in physical design and curricular program, enabling active AS child to adjust to the school environment. Individualization and flexibility are important factors. Consistent behavior modification in the school and at home can enable the AS child to be toilet trained (schedule- trained), and perform most life skills related to eating, dressing and performing general activities in the home.

Resources Angelman Syndrome Foundation, Inc. Angeland “Angelman Syndrome” Asclepius Online.