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Angelman syndrome (AS) is a genetic
disorder which causes severe developmental delay. The most striking
symptoms are mental retardation, a severe speech disorder (in most
cases, lack of speech), gross and fine motor difficulties, a short
attention span as well as some behaviorally unique features such
as hand flapping, hypermotoric behavior, an easily excitable personality
and a frequently happy demeanor. In addition, some individuals with
AS exhibit a suck/swallowing disorder and/or frequent tongue thrusting,
sometimes accompanied by drooling. Other common features include
wide-spaced teeth and hypopigmentation (lighter skin and hair than
their family members). (also see Consensus Criteria below and search
our database of subjects, who include a wide range of ages, backgrounds,
ethnicities, and genetic diagnoses)
Overview of Issues
Some of the most difficult issues faced by families and caregivers
include the common onset of seizures during childhood, a difficult
sleep pattern (individuals with AS often seem to need hardly any
sleep at all), and communication. Communication is an especially
complex issue, because even though most AS individuals don't have
any speech at all, they understand a lot of what is said to them.
In order for them to be able to express themselves, alternative
methods of communication have to be established, which can be a
long and difficult process. The issue of communication is explored
in depth as part of The Angelman Project. Other important topics
explored in The Angelman Project include schooling, housing and
job/activity provision for adults, behavioral issues and physical
therapies, among others. (Search our database for in-depth information
and CD collections on all these issues)
Genetic Background
Angelman syndrome is caused by a missing or "faulty" genetic code
on chromosome #15. To date, there are four distinct known genetic
causes for AS that can be determined by genetic testing. These four
separate diagnoses, which all cause the same syndrome, but with
some variations in the symptoms, are as follows: deletion+, uniparental
disomy (UPD), imprinting and UBE3A, which is the only hereditary
diagnosis. For more detail, please see the Genetics section below
or refer to films featuring Dr. Jill Clayton-Smith and Dr. Charles
Williams.
Diagnosis/testing "Consensus clinical diagnostic
criteria for AS have been developed, but the mainstay of diagnosis
testing is: 1) analysis of parent-specific DNA methylation imprints
in the 15q11-q13 chromosome region, which detects ~78% of patients
with AS, including those with a deletion, uniparental disomy, or
imprinting defect; and 2) mutation analysis of the UBE3A gene, which
detects an additional ~11% of patients. Less than 1% of patients
have a cytogenetically visible chromosome rearrangement. The remaining
~11% patients with classic phenotypic features of AS have a presently
unidentified genetic mechanism and thus are not amenable to diagnostic
testing."
Genetic counseling "AS is caused by the
loss of maternally imprinted contribution(s) in the 15q11-q13 (AS/PWS)
region that can occur by at least five different known genetic mechanisms.
The risk to sibs of an affected child of having AS depends upon
the genetic mechanism of the loss of the maternally contributed
AS/PWS region. The risk to sibs of an affected child who has a deletion
or uniparental disomy is typically <1%. The risk is as high as 50%
to the sibs of a child with an imprinting defect or a mutation of
the UBE3A gene. Members of the mother's extended family are also
at increased risk when an imprinting defect or a UBE3A mutation
is present. Cytogenetically visible chromosome rearrangements may
be inherited or de novo. Prenatal testing is possible when the underlying
genetic mechanism is deletion, uniparental disomy, imprinting defect,
UBE3A mutation, or chrosmosome
rearrangement."*
*"Angelman Syndrome" Authors: Charles A Williams, MD; Amy C Lossie
; Daniel J Driscoll, PhD, MD Initial Posting: 15 September 1998
Last Update: 21 November 2000 In: GeneReviews at GeneTests·GeneClinics:
Medical Genetics Information Resource (database online). Copyright,
University of Washington, Seattle. 1997-2002. Accessed 8.21.02.
Available at www.GeneClinics.Org
or www.GeneTests.Org
Consensus Criteria or Clinical Symptoms
of Angelman Syndrome
The following is an official list of the clinical characteristics
of Angelman syndrome. These were derived by Dr. Charles Williams,
er al, through the study of a group of individuals with AS and are
known as "consensuscriteria".
A. Consistent Characteristics (100%)
o Developmental delay, functionally severe
o Speech impairment, none or minimal use of words; receptive and
non-verbal communication skills higher than verbal ones
o Movement or balance disorder, usually ataxia of gait and/or tremulous
movement of limbs
o 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 Characteristics (more than 80%)
o Delayed, disproportionate growth in head circumference, usually
resulting in microcephaly (absolute or relative) by age 2
o Seizures, onset usually < 3 years of age
o Abnormal EEG, characteristic pattern with large amplitude slow-spike
waves (usually 2-3/s), facilitated by eye closure
C. Associated Characteristics (20 - 80%)
o Flat occiput (back of head)
o Occipital groove
o Protruding tongue
o Tongue thrusting; suck/swallowing disorders
o Feeding problems during infancy
o Prognathia (projecting jaw)
o Hypopigmented skin and eyes
o Wide mouth, wide-spaced teeth
o Frequent Drooling
o Excessive chewing/mouthing behaviors
o Strabismus
o Hypopigmented skin, light hair and eye color (compared to family),
seen only in deletion cases
o Hyperactive lower limb deep tendon reflexes
o Uplifted, flexed arms during walking
o Increased sensitivity to heat
o Sleep disturbance
o Attraction to/fascination with water
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