A genetic disease which appears to be to be the genetic
counterpart to Prader-Willi Syndrome
, with the opposite
pattern of imprinting
(maternal imprinting for Angelman, paternal for Prader-Willi).
The Angelman phenotype
was first described by French
doctors Bower and Jeavons in 1967 as "happy puppet" children ('marionette joyeuse
'), due to the unusual gait and mannerism
s of patient
s. The gait ataxia
seems to be the result of unusual electrical activity in the brain, somewhat like low-grade epileptic seizure
s. Some of the earliest described patients had convulsions and episode
s of flapping their arms up and down with elbow
s bent (like a puppet on strings, leading to the name of the disease), as well as uncontrollable laughter. Other general features of the disease are hypopigmentation compared to relatives, a tendency
of the tongue
, and severe
(speech absent, or limited to 6 words or less).
Angelman Syndrome is inherited through maternal imprinting
of the long arm of chromosome 15. The most common mechanism
is as a deletion
of bands 15q11-q12 inherited from the mother (note, this is the same exact region as Prader-Willi Syndrome
, but with maternal imprinting).
Because the disease phenotype is the result of chromosomal abnormal
ities, most cases are sporadic
in nature, arising
without previous family history
. As such, the risk of recurrence
is very low, considered to be about 1 in 1000.
As an aside
, the mouse model
for AS has a very interesting
ing many of the neurological
defects of AS sufferers. The mouse is highly sensitive to sound, going into seizures at any sharp noise. In fact, the lab in which I worked accident
ally killed the very first Angelman mouse we made in this exact manner while video taping
it. The camcorder
tapping against its cage caused the mouse to seize
uncontrollably until it died.