Elsevier

Epilepsy Research

Volume 47, Issues 1–2, November 2001, Pages 119-126
Epilepsy Research

Epilepsy and trisomy 19q—different seizure patterns in a brother and a sister

https://doi.org/10.1016/S0920-1211(01)00303-5Get rights and content

Abstract

In symptomatic epilepsies due to chromosomal aberrations, epileptogenesis may be either the direct consequence of deletion or duplication of a gene causing seizures or may have a more complex etiology caused by the disturbance of the interaction of several genes and environmental factors. We report on a brother and a sister with trisomy 19q13.3→qter who present different epileptologic features and discuss epileptogenesis in this syndrome with respect to genes known to be located on the distal part of chromosome 19q. Both patients share mental retardation and several dysmorphic features. The boy was hypoxic at birth and showed an extremely delayed psychomotor development. The girl, however, had no significant neonatal problems, and her psychomotor development was better. Although the male had an abnormal EEG in childhood, his first partial seizures occurred only as late as at age 31 years. He subsequently became seizure-free with carbamazepine (CBZ). In contrast, the girl already suffered from absence-like seizures during childhood and became seizure-free under ethosuccimide (ESM). A photoparoxysmal response, however, is still visible in her EEG. The difference between the epileptologic features in these siblings points to epileptogenic mechanisms placed far downstream on the way from genotype to phenotype. The photoparoxysmal response—otherwise a facultative finding in genetically determined epilepsies—in the EEG of the sister, however, points to a closer relationship between the duplicated genes and epileptogenesis. The fact that genes encoding potassium channels are located on 19q13.3–q13.4 may also support the latter assumption.

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.

References (27)

  • C.D. Binnie et al.

    Photosensitivity as a model for acute antiepileptic drug studies

    Electroenceph. Clin. Neurophysiol.

    (1986)
  • J. Aicardi et al.

    Le syndrome spasmes en flexion, agenesic calleuse, anomalies chorio-retiniennes

    Arch. Franc. Pediat.

    (1969)
  • A. Battaglia et al.

    The inv dup (15) syndrome: a clinically recognizable syndrome with altered behavior, mental retardation, and epilepsy

    Neurology

    (1997)
  • C. Biervert et al.

    A potassium channel mutation in neonatal human epilepsy

    Science

    (1998)
  • C.D. Binnie et al.

    Photosensitive epilepsy: clinical features

  • E.B. Bromfield

    Ethosuximide and other succinimides

  • H. Doose

    Myoclonic astatic epilepsy of early childhood

  • C. Dravet et al.

    Benign myoclonic epilepsy in infants

  • C. Dravet et al.

    Severe myoclonic epilepsy in infants

  • F. Elmslie et al.

    Epilepsy and the new genetics

  • Entrez Genome, Center for Medical Genetics, Johns Hopkins University (Baltimore, MD) and National Center for...
  • R. Guerrini et al.

    Chromosomal abnormalities

  • G.F. Harding et al.

    Persistence of photosensitivity

    Epilepsia

    (1997)
  • Cited by (16)

    • Elongated Conus Medullaris, Sacral Agenesis, and Scoliosis: A Case Report of a Patient with Trisomy 19q and Monosomy 7q

      2019, World Neurosurgery
      Citation Excerpt :

      The mosaic image of deletion of the subtelomeric region in the q-arm of chromosome 7 is superimposed by the duplication of the subtelomeric region in the q-arm of chromosome 19. The cases of trisomy on subtelomere 19q described in the literature are characterized by low birthweight, small body size, atypical ears, short neck, intellectual retardation, delayed motor development, and delayed speech development.8-10 Monosomy at subtelomere 7q again shows a phenotype with growth retardation, facial shape abnormalities, and mental retardation.11,12

    • 19q13.33→qter trisomy in a girl with intellectual impairment and seizures

      2014, Meta Gene
      Citation Excerpt :

      Rearrangements involving chromosome 19, either duplications or deletions, have rarely been reported. The main clinical features in partial 19q trisomy include low birth weight, short stature, abnormal ears, short neck, intellectual disability and seizures (Dorn et al., 2001; Lenzini et al., 2010). Seven patients with pure 19q trisomy, and 28 patients with other concomitant chromosome imbalances, have been published.

    • Duplication 19q13-qter and deletion 19p13-pter arising from an inversion (19)(p13.3q13.3) of maternal origin

      2006, European Journal of Medical Genetics
      Citation Excerpt :

      The clinical effect is due to the combination of both imbalances, the trisomy 19q and the deletion 19p. Partial trisomy 19q has been reported in about 20 cases [2,5,12,15,16]. All but two de novo duplications have been due to unbalanced translocations.

    View all citing articles on Scopus
    View full text