Angleman Syndrome

Angelman Syndrome:Happy Puppet Syndrome

Jessica Nickels

Background Information

• In 1965, Dr. Harry Angelman discovered Angelman syndrome (AS).

• Was working with 3 children who all had a stiff, jerky gait, absent speech, excessive laughter, and

seizures.

• Angelman decided that the 3 children must have the same disorder using clinical data.

Background Information Cont’d

• He was unable to establish scientific proof due to lack of technology.

• His findings were pushed aside until the 1980’s when more research began to take place.

• The new technology discovered that AS was a genetic syndrome.

• Prevalence: 1 in 15,000

• about 300 reported cases (1993)

Genetic Basis of AS

• AS is caused by a deletion or mutation occurring in chromosome 15

• 4 Main Causes:– ~70% caused by deletion of part of the maternally

contributed chromosome 15

– ~5% caused by mutation of UBE3A (a protein) within the maternally contributed chromosome 15

Genetic Basis of AS

– ~5% caused by a paternal uniparental disomy

• the child inherits both copies of chromosome 15 from father

– ~4% child inherits chromosome 15 from both

parents but the copy inherited from the mother

functions the same way that a paternal

chromosome 15 should function

Clinical Confusion

• AS is often misdiagnosed as Prader Willi syndrome (PWS) because of similar clinical signs

• PWS and AS are two clinically distinct disorders, but they are both caused by an absence that occurs in chromosome 15.

• PWS results from an absence that occurs in the paternal chromosome 15 while AS occurs in the maternal chromosome 15.

Clinical Features of AS

• 100%

– Functionally severe developmental delay,

– Speech impairment, lack of speech 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


• 100% Continued

– Any combination of frequent laughter/smiling;

apparent happy demeanor; easily excitable

personality

– hand flapping movements; hypermotoric behavior;

short attention span


• ~80%– Delayed, disproportionate growth in head

circumference

– Seizures, onset usually before 3 years of age

– Abnormal EEG


• ~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


• ~20- 80% (continued)

– Excessive chewing/ mouthing behaviors

– Strabismus (squinting of eye)

– Hypopigmented skin

– Hyperactive lower limb deep tendon reflexes

– Uplifted, flexed arm position especially during

ambulation

– Increased sensitivity to heat

– Sleep disturbance

– Attraction to/ fascination with water

Growth and Development

• Seizures– Methods of treatment vary from different

medications to ketogenic diet

– can happen at any time

• Gait & Movement Disorders– jitteriness present in first 6 months

– slight jerkiness and uncoordinated movements prevent walking, feeding, and reaching for objects.

– Sitting usually occurs after 12 months and walking is delayed until age 3 or 4 years

Growth and Development

• Puberty– generally normal in adolescence– reproduction is possible for both males and

females• no cases have been documented

• Speech– language impairment is severe– appropriate use of even one or two words is

rare– few can learn sign language– most are able to use their own sign language

to communicate

Growth and Development in adolescents and adults

• Clayton-Smith J. Angelman syndrome: evolution of the phenotype in adolescents and adults. Dev Med & Child Neur. 2001;43: 476-480

• Study looked at 28 adolescents and adults and their clinical features

• Concluded:– facial features: elongation of face more prominent

– scoliosis apparent, mobility decreased

– seizures decreased

– ataxic gait less obvious

– hyperactivity reduced

– communication skills improved - signing

Problems Relating to Nutrition

• Nutrition problems often first present to the physician as poor weight gain or failure to thrive and not as sign of AS

• Feeding Problems– difficulty sucking or swallowing

• may be trouble initiating sucking and sustaining breast feeding

• bottle feeding may be easier• most are hypotonic (diminishing muscle

mass)

Problems Relating to Nutrition

• Feeding problems continued

– tongue thrusting• causing difficulty to keep things in mouth

(i.e. food or bottles)

– gastroesophageal reflux• may require surgery

– Many AS children experience constipation.

– Obesity in older patients- due to lack of mobility

Feeding Characteristics

• Sucking and/or tongue thrusting, frequent

spitting up improves in time

• Some children seem to begin finger feeding at an

appropriate age, and parents report that they

can’t seem to shovel it in fast enough.

– As child gets older, eating speed slows

• Parents have to choose lower fat items or limit

serving size because of fear of obesity


• AS children have high caloric intake; however, the children remain thin

– due to high metabolism and hyperactivity

• Introducing spoon feeding can be difficult!

– Children feels using a spoon is too slow.

– One parent reported that she needed to hold one hand down for a long time before the child would try the spoon with the other hand.

– Child learned to use the spoon quite quickly and well

– However, finger feeding was the method of choice when left unsupervised!


• Food choices in younger children with chewing difficulties were geared towards texture of foods as well as taste

Conclusion

• With attentive care, children with AS are capable to learn to communicate and feed themselves.

• Main nutrition problems to look at are reflux and obesity.

• Further research needs to be done to learn more about the nutritional risk for AS children

Any Questions?

Documents

Angleman Syndrome