Partial Trisomy 18q and Epileptic Spasms Induced by Eating Associated With Bilateral Opercular Dysplasia

Abstract

In2007,wedescribedtheclinicalandvideo-polygraphicfeaturesofa patient with reflex periodic spasms triggered by eating [d’Orsietal.,2007].Thepatientwasa30-year-old,right-handedmanwithsevereasphyxiaatbirthandsignificantintellectualdisability.Fromthe age of 25, he began to experience generalized tonic–clonicseizures,atonicdropattacksandeating-inducedrepetitiveepilepticspasmscharacterizedbysuddenheadandupperlimbsdropping.Inparticular, during the longer spasms (at least 1sec) the ictalpolygraphy showed a diffuse slow wave complex prevalent onanterior regions with an activation in crescendo-decrescendo onthe neck and the right sternocleidomastoideus muscles. Subse-quently, chromosome analysis, fluorescence in situ hybridization(FISH), and array comparative genomic hybridization (array-CGH) were performed. The array-CGH was carried out usingthe GenomeARRAY slide (TechnoGenetics Srl-Bouty Spa, Italy),containing 5,380 BAC clones, with a genomic resolution ofabout 0.5Mb, and increasing to 0.25Mb in the subtelomericregions. These studies revealed the presence of a partialtrisomy of chromosome 18 in the 18 q12.2q22.3 region (partialtrisomy 18q; see Fig. 1). The parents had normal karyotypes andarray-CGH.The relationship between chromosomal 18 anomalies and epi-lepsy was evaluated in a previous review [Grosso et al., 2005], andpartial seizures and focal EEG abnormalities were observed inpatients with 18 qDS, trisomy 18p and translocation betweenchromosome17and18.Epilepsyonsetinpatientscarryingtrisomy18p is usually during infancy, and focal seizures remitted in themajority. EEG pattern disclosed symmetric or asymmetric parox-ysmal activity in posterior regions associated with generalizedspikes and spike and waves, while brain MRI showed agenesis ofthe splenium and thin of corpus callosum.Toourknowledge,nopreviouscaseshavebeenreportedregardingthe relationship between partial trisomy 18q and epilepsy, andour patient expands the clinical spectrum and genomic character-izationoftrisomy18.Infact,fromaclinicalpointofviewageseizureonset (25 years) and seizure semiology (epileptic spasms inducedbyeating)differentiateourcasefromothersreportedintheliterature-[Grosso et al., 2005]. In addition, genetic testing based on array-CGH and FISH have revealed additional material on chromosome18, specificallya partialduplication of the longarm of chromosome18 (trisomy of 18q12.2q22.3 region), not previously associatedwith epileptic phenotype. Deletion of genes located in the distalportion of 18q seems to be important in conferring susceptibilityfor the clinical features, including epilepsy [Strathdee et al., 1995].Deletion of the long arm of the chromosome 18 is associated withepilepsy witha frequency ranging from 10% [Wilson et al., 1979] to31%[Strathdeeetal.,1995].Notablythepatientshavebeenreportedin the literature with partial duplication of the short arm of chro-mosome 18 and epilepsy, but no previous cases have been reported