Angelman

etiology
60-80% of pt's have interstit delet of 15q bands 11-13
origin of deleted chromosome is maternal (mnemonic: girls are angels, boys are hungry devils)
"genomic imprinting" = genes on 15q11q13q on maternally inherited chromosome are expressed differently from paternally inherited xsome
paternal uniparental disomy is a rare cause of the d/o
all cases are sporadic with exception of familial chromosomal rearrangement of Angelman locus

main features ("left handed, laughing puppet")
"puppet-like" gait
paroxyms of laughter
characteristic facies

abnormalities
Development: severe MR with motor delay (100%); profound speech deficit: absent speech or <6words
Head/Facies: microbrachycephaly; blond hair (65%); ocular abnormalities (decreased choroid/iris pigmentation -> resulting in pale blue eyes); deep set eyes; large mouth (macrostomia) protruding tongue/widely spaced teeth; maxillary hypoplasia and prognathia (prominent chin)
Coloring: ocular or skin hypopigmentation (pale eyes).
Behavior: paroxysms of inappropriate laugher often accompanied by hand flapping; hyperactivity; ataxia/jerky arm movemts (~ puppet gait; 100%, becomes apparent around time child begins to sit); arms in characteristic position (upheld with wrist/elbow flexion)
Neuro stuff: seizures (variable type; usually begin 18-24mos; 86%; relatively easy to control); characteristic EEG findings; hypotonia c occas hyperreflexia; cerebral atrophy (33%)
L hand preference

natural hx
MR is nonprogressive but severe
sz's most severe ~4yrs; may stop by 10yrs
laughter NOT assoc c happiness but probable brain stem abnL
decr sleep from 2-6yrs
vast majority communicate nonverbally (eg, sign language)
may be able to follow simple commands

Smith's
CHLA board review course 2005
Baraitser and Winter, 1996. Color Atlas of Congenital Malformation Syndromes