CLINICAL-FEATURES IN 27 PATIENTS WITH ANGELMAN SYNDROME RESULTING FROM DNA DELETION

We report the clinical features in 27 Australasian patients with Angel man syndrome (AS), all with a DNA deletion involving chromosome 15(q11 -13), spanning markers from D15S9 to D15S12, about 3.5 Mb of DNA. Ther e were nine males and 18 females. All cases were sporadic. The mean ag e at last review (end of 1994) was 11.2 years (range 3 to 34 years). A ll patients were ataxic, severely retarded, and lacking recognisable s peech. In all patients, head circumference (HC) at birth was normal bu t skewed in distribution, with 62.5% at the 10th centile. At last revi ew HC was around the 50th centile in three patients (12.5%) while 15 h ad poor postnatal head growth. Short stature was not invariable, 5/26 (19%) were on or above the 50th centile. Hypotonia at birth was record ed in 15/24 (63%) and neonatal feeding difficulties were recorded in 2 0/26 (77%). Epilepsy was present in 26/27 (96%) with onset by the thir d year of life in 20 patients (83%). Improvement in epilepsy was repor ted in 11/16 patients (69%) with age. An abnormal EEG was reported in 25/25 patients. Hypopigmentation was present in 19/26 (73%). One patie nt had oculocutaneous albinism. Five patients could not walk independe ntly. Of the remaining 22 who could walk, age of onset of walking rang ed from 2 to 8 years. Disrupted sleep patterns were present in 18/ 21 patients (86%), with improvement in 9/12 patients (75%) over 10 years of age. The clinical features in this group of deletional AS patients were similar to previous reports, but these have not separated patient s into subgroups based on DNA studies. In our group of deletional case s, 100% showed severe mental retardation, ataxic movements, absent lan guage, abnormal EEG, happy disposition (noted in infancy in 95%), norm al birth weight and head circumference at birth, and a large, wide mou th. These features occurred with a higher frequency than in AS patient s as a whole. Our study also provided information on the evolution of the phenotype. The data can act as a benchmark for comparisons of AS r esulting from other genetic mechanisms.