Abstracts

Rationale: Subcortical band heterotopia, also called double cortex, is a malformation of brain cortical development due to deficient neuronal migration. It is classically due to either DCX or LIS1 gene mutations, respectively for a more prominent anterior or posterior distribution of the SBH. Methods: Review of our database of adult epilepsy patients with subcortical band heterotopia for which no DCX or LIS1 mutation was found. Results: Fifteen patients presenting with various degrees of epilepsy, with or without an associated cognitive delay, had a subcortical band heterotopia (SBH) for which no DCX or LIS1 mutation was found. They had no associated pachygyria. They were all sporadic patients. They were evaluated with a karyotype and DCX and/or LIS1 mutation analysis, depending on the pattern of the distribution of their SBH. A few patients had both DCX/LIS1 sequencing and deletion/duplication analysis when their SBH was diffuse. In one woman, the karyotype showed a rearrangement of chromosome 9 suggesting a paracentric inversion of the q13->q22.3 region. Karyotype analysis in both parents was normal, indicating a de novo chromosomal rearrangement in the proband. This patient had a history of infantile spasms, morning myoclonus seizures and pervasive developmental delay. She presented a thick and diffuse SBH. Her DCX/LIS1 sequencing and deletion/duplication analysis were negative. A CGH microarray (with 135000 oligonucleotides) was added and did not reveal any deletion or duplication. A higher resolution CGH microarray is planned in order to evidence a possible micro deletion or duplication. Conclusions: Genetic evaluation of SBH deserves a DCX or/and LIS1 sequencing and deletion/duplication analysis but does not always reveal the genetic cause of this brain malformation. Karyotype analysis may still be of interest in these unsolved cases. Careful analysis of other sporadic SBH patients, as well as familial cases, negative for DCX/LIS1 evaluation, is mandatory in order to elucidate their genetic cause and improve genetic counselling.