Abstracts

Inverted duplication of chromosome 15 [inv dup(15)] is associated with phenotypic abnormalities, mental retardation, behavioral profile and epilepsy. Phenotypic traits are mild and for this reason delineation of epilepsy and behavior is important. Studies that attempt to elucidate the electroclinical phenotype and possible genotype correlation reveal severe epilepsy associated with large duplication in the PWS/AS region. Herein, we analyze the electroclinical phenotype in our inv dup(15) patients, comparing with published data, in an effort to define the electroclinical spectrum and which genetic factors are implied in its severity.
Clinical investigation was carried out with questionnaire applied to relatives. Further information was added by file revision, contact other physicians and V-EEG. All patients were submitted to prolonged EEG studies. Review of previous EEG obtained in early ages was also done. Cytogenetic and molecular analysis was conducted using FISH test. Psychiatric diagnosis was done using DSM-IV.
Chromosome studies by GTG banding and FISH revealed a large sized inv dup(15) in all patients. The analysis of SNRPN methylation pattern showed one paternal and one maternal band, excluding the AS/PWS diagnosis. All patients had autism. Seizures started in infancy (2 to 6mo) with infantile spasms; but evolution was variable. The 1st patient (20y) had a period of refractoriness during childhood and now presents rare atypical absences and TCG seizures. She presented normal EEGs up to the age of 9y, when she presented frequent epileptiform discharges (ED) over the left temporal region.The 2nd patient (7y) was controlled with vigabatrin and remains for 6y without seizures of which the last 3y without AED. His EEG disclosed hypsarrhythmia (9 mo), evolving to multifocal ED (1y) and now ED over parasagital regions. The 3rd patient (14y) has severe and refractory epilepsy with daily tonic seizures and drop attacks. EEG obtained at different ages (6y-14y) demonstrates frequent runs of high amplitude fast activity during sleep and generalized and irregular spike and polyspike-and-wave complexes during wakefulness.
Study of electroclinical profiles in chromosomal disorders is emphasized, due to its importance for diagnosis, mainly in those with a mild phenotype such as inv dup(15). However, analysis of our patients, plus review of published data, demonstrates that, except for the presence of generalized epilepsy starting with infantile spasms, the binomial epilepsy-EEG was not stereotyped enough to corroborate and support this difficult diagnosis. In our patients, size of the inv dup(15) did not represent pivotal factors to determine severity, since all patients presented large sized markers apparently the same breakpoints, which may demonstrate that the genotype-phenotype correlation is more complex than previously thought.