Abstracts

Rationale: Duplications of chromosome 15q (q11.2-q13) are a common cause of autistic spectrum disorders (ASD). The two major categories of duplications are interstitial duplications (or triplications) and isodicentric chromosome 15q (idic15). While ASD is common in both subtypes, those with idic15 typically have a much more severe phenotype, often associated with motor delays and seizures. While the presence and severity of ASD has been well documented in this population, the presence, severity and semiology of seizures associated with these chromosomal abnormalities has not been well studied. Methods: Medical histories from 6 children in our Pediatric Epilepsy Program with chromosome 15q duplications were reviewed for the presence, frequency and semiology of seizures, autistic features and EEG findings. This small sample will serve as a pilot study for a much larger study assessing epilepsy in this population. Results: There were three children, ages 3-8, with interstitial chromosome 15q duplications, 2 with standard duplications and one with a duplication/triplication mosaic. None of the 3 has experienced clinical seizures but all 3 have mild ASD, with the individual with the mosaic displaying more severe features of ASD. Two of the three had mild, non-epileptiform EEG abnormalities during sleep, but all had normal background waking frequencies. There were also three children, ages 7-10, with idic15 who all had clinical epilepsy and moderate to severe ASD. All 3 children experienced atypical absence seizures and two of the three also had atonic seizures with two having a history of infantile spasms. All three children have been refractory to >2 antiepileptic medications. The EEG findings for the two children who had EEGs showed background slowing with slow (2-3 Hz) generalized spike and wave activity with one of the EEGs also showing multifocal discharges. Conclusions: Duplications of chromosome 15q are a common cause of ASD and all 6 children in this sample had some degree of ASD, with those with interstitial duplications exhibiting milder phenotypes. None of the three children with interstitial duplications had clinical seizures or epileptiform activity on EEG, while all three of the children with idic15 had refractory epilepsy. These epilepsies appeared to be mainly generalized epilepsies with atypical absence and atonic seizures being the prominent seizure types (with two of three having a history of infantile spasms) and generalized slow spike and wave discharges noted on EEG. The sample is too small to assess the relationship between seizures and autistic features. This data will serve as the basis for an upcoming study of a large population of individuals with chromosome 15q duplications assessing the frequency, severity and semiology of seizures in these individuals as well as current treatments for these seizures. In addition, this study will examine the relationship between seizures and the presence and severity of ASD as well as associated EEG findings.