Epilepsy and trisomy 19q—different seizure patterns in a brother and a sister
Introduction
Many chromosomal aberrations may cause epileptic seizures (Elmslie and Gardiner, 1997, Guerrini et al., 1997, Nance et al., 1997). However, it is difficult to understand the epileptogenesis in these diseases because the chromosomal aberration (deletion, duplication, triplication) comprises not only one, but many genes. In addition, not only genetic factors but also environmental conditions and acquired brain injuries may contribute to phenotype ‘seizures’. For example, in trisomy 21 epileptic seizures occur in only about 1–10% of affected persons (Elmslie and Gardiner, 1997, Guerrini et al., 1997) whereby especially patients with additional perinatal asphyxia, hypoxia due to congenital heart disease or infection developed epilepsy (Stafstrom et al., 1991). Nevertheless, there are some chromosomal disorders in which epileptogenesis may be closely related to proteins encoded by the involved genes. For example, in partial tetrasomy 15 (pter-q13) due to an additional inv dup (15) chromosome a relationship between triplication of genes encoding GABAA-receptor subunits and the severe epilepsy being typical in this syndrome has been discussed (Battaglia et al., 1997). Thus, despite the above-mentioned difficulties, chromosomal aberrations offer the opportunity to study the role of genes of proteins which proved or seem to be relevant in neurobiological models of epileptogenesis in human epilepsies.
We present a brother and a sister with trisomy of the distal part of the long arm of chromosome 19 showing different epileptologic symptoms, compare our data with those of other cases of trisomy 19q from the literature and discuss the possible role of some potassium channels genes mapping within the duplicated region (KCNC3, KCNC2, KCNA7) (Entrez Genome, 2000, http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez; OMIM, 1998, http://www.ncbi.nlm.nih.gov/omim) in the epileptogenesis of our patients.
Section snippets
Case reports
The boy was born at 38 weeks of gestation with a weight of 2.500 g and length of 42 cm. Birth was prolonged with signs of asphyxia after an uneventful pregnancy. During first weeks of life he suffered from recurrent urinary infections. At age 34 years, his height was 1.39 m, weight was 40 kg and occipito-frontal head circumference (OFC) was 52 cm (all measurements far below the 3rd percentile). He showed brachycephaly, narrow palpebral fissures in slightly antimongoloid position, a flat
Cytogenetic investigations and results
GTG-banded metaphase lymphocyte chromosome examinations revealed a 20p+ chromosome in both probands. Subsequent examination of the parental chromosomes disclosed a balanced translocation between 19q and 20p in the mother. Her karyotype was 46, XX, t(19;20)(q13.3;pter) (Schmid, 1979). Recently, cultivated lymphocytes of the probands were again investigated using GTG-banding. The karyotypes were 46, XX, der(20)t(19;20)(q13.3;pter) and 46, XY, der(20)t(19;20)(q13.3;pter), respectively. The mother
Discussion
In the male proband seizures started at the age of 31. Both semiology, interictal EEG findings, and seizure freedom under CBZ support classification of epilepsy as focal. Since there were no clinical reasons for performing MRI which would have been only possible under general anesthesia in this mentally retarded and restless patient, we have no information about the nature of a possible epileptogenic lesion. With CBZ there was no photoparoxysmal response in the EEG. Unfortunately, for technical
Acknowledgements
The FISH workup was supported by the Swiss National Foundation, grants Nr. 32-45604.95 and 32-56051.98 to A.S. and M.R.
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