Clinical features in27patients withAngelman syndrome resulting fromDNA deletion

We report theclinical features in27Australasian patients withAngelmansyndrome (AS),allwitha DNA deletion involving chromosome15(qll-13), spanningmarkersfromD15S9to D15S12, about3*5Mb ofDNA. Therewerenine malesand18females. Allcasesweresporadic. Themeanageatlastreview(endof 1994) was11*2years(range 3to34years). Allpatients wereataxic, severely retarded, andlacking recognisable speech. Inall patients, headcircumference (HC)atbirth wasnormalbutskewedindistribution, with62-5%atthe10thcentile. AtlastreviewHC wasaroundthe50thcentile in threepatients (12-5%) while15hadpoor postnatal headgrowth. Shortstature was notinvariable, 5/26(19%) wereonorabove the50thcentile. Hypotonia atbirthwas recorded in15/24 (63%)andneonatal feedingdifficulties wererecordedin20/26 (77%). Epilepsy waspresent in26/27 (96%) withonsetbythethirdyearoflife in20 patients (83%). Improvement inepilepsy wasreported in11/16 patients (69%)with age.An abnormalEEG wasreported in 25/25patients. Hypopigmentation was present in19/26(73%).Onepatient had oculocutaneous albinism. Fivepatients couldnotwalkindependently. Oftheremaining 22whocouldwalk,ageofonset ofwalking rangedfrom2to8years. Disruptedsleep patterns werepresent in18/ 21patients (86%), withimprovement in9/ 12patients (75%)over10yearsofage. The clinical features inthisgroupof deletional ASpatients weresimilar toprevious reports, butthese havenotseparated patients intosubgroups basedon DNA studies. Inourgroupofdeletional cases, 100%showedseverementalretardation, ataxic movements,absentlanguage, abnormalEEG,happydisposition (noted in infancy in95%),normalbirthweightand headcircumference atbirth, andalarge, widemouth.Thesefeatures occurred with ahigher frequency thaninAS patients as a whole.Our studyalsoprovided information ontheevolution ofthephenotype. Thedatacanactasabenchmarkfor comparisons ofAS resulting fromother genetic mechanisms. (JMedGenet1996;33:107-112)