Abstracts

Rationale: Chromosome (chr) 6q deletion syndrome has been delineated into three distinct phenotypes corresponding to proximal (6q11-16), interstitial (6q15-25) and terminal deletions (6q25-qter). Epilepsy associated with 6q terminal deletions has recently been recognized as a new entity characterized by autonomic symptoms and focal epileptic activity over one or both posterior quadrants. We wish to report the clinical, epilepsy, and array CGH characterization in a woman with interstitial 6q deletion, febrile seizures and absences, and compare it to our previously reported patient with interstitial 6q deletion and adult onset of myoclonic epilepsy (Andermann E et al., Epilepsia 2008, 49(Suppl.7):309-310). Methods: Detailed review of medical records; oligonucleotide microarray analysis of genomic DNA; and fluorescence in situ hybridization (FISH) analysis to confirm the deletions. Results: A 22-year-old woman, product of an uneventful fullterm pregnancy, had initially normal developmental milestones but speech development was delayed at age 4. She developed febrile seizures at age 3, and later absence attacks, relatively well controlled with valproic acid. Evaluation showed mild mental deficiency, generalized epileptiform discharges on EEG, and at age 13 mild left occipital periventricular leukomalacia on MRI. At age 22, she had upslanting eyes and narrow palpebral fissures, notched eyebrows, micrognathia, microcephaly and short stature, mild mental retardation, and absences poorly controlled by valproic acid and topiramate. She was also treated for hypothyroidism. A standard karyotype at 4 years revealed a chr6q deletion. Microarray analysis detected a single copy loss of 360 oligonucleotide probes at 6q22.1-22.33 (12.8 Mb, at least 32 OMIM genes), confirmed by FISH. A 31-year-old man, born after an uneventful fullterm pregnancy had a febrile seizure at age 8 months and developmental delay. At age 14, two hair whorls, small forehead with low frontal hairline, head circumference at 3rd percentile, mild retrognathia, hyperextensible joints, and mild quadriparesis were recorded. In his late twenties, he developed stimulus-sensitive myoclonic jerks that increased in frequency over the past three years. Evaluation showed slow background rhythm, no ictal or interictal epileptic abnormalities, and mild cerebellar vermian atrophy or hypoplasia. Cytogenetic studies at one year of age were reported as normal and at age 30 revealed chr6q22.1-22.2 deletion. Microarray analysis detected a de novo single copy loss of 164 oligonucleotide probes at 6q21-22.31 (7.6 Mb, at least 18 OMIM genes), confirmed by FISH. Conclusions: Chr6q interstitial deletions can be associated with a different epilepsy phenotype (febrile seizures, absences and myoclonus) from that associated with 6q terminal deletions. In one reported GEFS+ pedigree with 15 affected individuals, a novel locus has been mapped to chr 6q16.3-22.31 (Poduri et al., Epilepsia 2008,49(Suppl.7): Abstract 2.351). Our results suggest that this locus might be narrowed to 6q22.1-22.31.