ANGELMANS SYNDROME (Happy Puppet Syndrome)

ataxic puppet-like gait absent speech paroxysms of laughter characteristic facies Epidemiology 1 in 20,000 onset in 1st year of life M ! "enetics gene is #$E%& on chromosome 1' large common deletion ()0*+ deletion of maternal copy of #$E%& , "&$-$% gene (codes for "&$& receptor+ sporadic usually .ithout apparent increased risk in future offspring usually diagnosed by !/01 microdeletion of maternal copy of #$E%& can occur in se2eral areas including imprinting centre and #$E%& gene can be sporadic or inherited from apparent normal mum if these deletions also present in mother '0* risk to offspring #$E%& mutations or imprinting mutation .ithin putati2e &0 gene imprinting normally maternal gene on if imprinted methylated s.itched off like a mutation or deletion appear sporadic if inherited from apparently normal mother risk of '0* transmission ho.e2er paternal #34 ('*+ appear sporadic .ith recurrence risk only 1*

genetic analysis methylation analysis fast and easiest5 at locus 41'06% distinguish maternal from paternal origin using methylation sensiti2e restriction endonuclease 1pa // due to methylation of maternal locus this test in2ol2es a southern blot (47&+ detect 80* of &0 but usually does not distinguish the mechanism maternal deletion, paternal #34, or imprinting mutation deletion of maternal origin (absent 6 9bp 1ind ///:1pa /// fragment+ !/01 analysis - .ill detect deletions $#; not #34 linkage analysis <linical features gro.th = normal /> - se2ere /> ? gross motor delay absent speech or @ 6 .ords beha2iour - hand clapping, tongue thrusting and mouthing, paroxysms of laughter (de2elop A %-B years of age+ face - time course of dysmorphism - absent at birth but becomes e2ident by ' years of age brachycephaly (short:broad-headed5 .ith cephalic index C805 cephalic index maximum breadth of the head to its maximum length x100+ pointed chin eyes - deep set eyes, blue eyes E7; - macrostomia (large mouth+ .ith prognathia, tongue protrusion, .ide spaced teeth M09 - small hands and feet scoliosis (10*+ onset by ' years of age and progressi2e skin = a:. hypopigmentation and oculocutaneous albinism (D<&2+ neuro - marked truncal hypotonia limbs (like #M7+ = hypertonia, flexion contracture , hyper-reflexic Eerky arm m2mts ataxia (puppet-like gait+ seiFures (begin in 2nd year of life+ /n2estigation <;:M-/ o mild cortical atrophy and generalised 2entricular enlargement 3rognosis

most reach adulthood se2erity of seiFures .ith age