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).
Clinical Features
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
mannerisms of
patients. The
gait ataxia seems to be the result of unusual electrical activity in the brain, somewhat like low-grade
epileptic seizures. Some of the earliest described patients had convulsions and
episodes of flapping their arms up and down with
elbows 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 to
protrude, and
severe mental
retardation (speech absent, or limited to 6 words or less).
Molecular Basis
Angelman Syndrome is inherited through
maternal imprinting of the long arm of chromosome 15. The most common
mechanism of
transmission 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
abnormalities, 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 phenotype,
exhibiting 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
accidentally 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.