Angelman syndrome without detectable chromosome 15q11-13 anomaly: clinical study of familial and isolated cases

The clinical findings in 12 Angelman syndrome (AS) patients (4 sib pairs and 4 sporadic cases, aged 12-55 years) without a cytogenetic or molecular detectable defect at the AS locus were compared to those of 28 AS patients (aged 11-50 years) with a deletion, in order to determine whether the clinical spectrum differed between the two groups. There were only two minor differences, i.e., mandibular prognathism was always found in the patients with a defect (100% vs. 58%), whereas truncal hypotonia was found less frequently in the group with a detectable genetic defect (54% vs. 91%). All other clinical and physical characteristics were equally represented in the two groups. Epileptic seizures occurred in 93% and 75%, respectively, of patients with and without a detectable chromosome 15 defect. Specific EEG patterns were found in 90% of both groups. The clinical signs and symptoms of our patients closely resemble those in familial AS cases reported in the literature, with the exception of scoliosis, which was present in 55% of the patients in our study. We conclude that the absence of a detectable cytogenetic or molecular defect at the AS locus is not associated with a strikingly different AS phenotype, compared to those with such a defect. Mutation analysis of the UBE3A gene in our patients without a detectable genetic defect, especially in the familial cases, is currently underway