Ring 14 chromosome presenting as early‐onset isolated partial epilepsy

Abstract

We report four infants (two males, two females) with ring 14 chromosome presenting with early‐onset partial epilepsy. The first seizure occurred between 3 and 6 months (3, 3, 4, and 6mo respectively). In all four cases, diagnosis was based on early focal seizures, rather than on psychomotor retardation or morphological features, which were not prominent at seizure onset. Moreover, despite the young age of the patients and the high frequency of seizures, neither epileptic spasms nor progression to ‘epileptic encephalopathy’, such as hypsarrhythmia, were observed. Epilepsy remained partial in these patients. At the most recent follow‐up, all four children had slight or mild psychomotor delay, and two of them had moderate non‐specific dysmorphic traits. Data from the literature about epilepsy in ring 14 chromosome syndrome were also reviewed. Ring 14 chromosome syndrome may be revealed by isolated, early‐onset focal epilepsy suggestive of focal lesions with only mild mental retardation and morphological features at the time of diagnosis. The characteristics of these observations differ from classic ring 14 syndrome, and may enlarge this clinical spectrum. Many unanswered questions remain concerning phenotype–genotype correlation and identification of the potential genes and molecular mechanisms responsible for epilepsy in patients with ring 14 syndrome.

Epilepsy in ring 14 chromosome syndrome

“…In relation to seizure semiology and EEG findings, presentation of epilepsy in our cases seems to be similar to that reported by Ville et al [28].…”

“…Electroencephalogram pattern is even more variable than seizure semiology. Ictal recordings have been reported [16,21,22,25,28,29] and findings are heterogeneous, as in our cases. The occurrence of either diffuse or focal discharges is not surprising in epilepsies related to chromosomal abnormalities.…”

Cytogenetic and molecular evaluation and 20‐year follow‐up of a patient with ring chromosome 14

“…However, our patient is now seizure free following treatment. The relatively constant clinical feature of seizures may manifest in various forms [Schlade-Bartusiak et al, 2005;Ville et al, 2009;Zollino et al, 2009], and usually appears between 1 month and 4 years of age [Zelante et al, 1991;Shirasaka et al, 1992;Ono et al, 1999;Morimoto et al, 2003]. Also, both patients reported by Morimoto et al [2003] and Ono et al [1999] showed generalized tonic-clonic convulsions that are similar to our patient and others reported in the literature as drug resistant.…”

“…Also, both patients reported by Morimoto et al [2003] and Ono et al [1999] showed generalized tonic-clonic convulsions that are similar to our patient and others reported in the literature as drug resistant. Some ring 14 patients may have epilepsy without prominent psychomotor retardation or morphological features [Ville et al, 2009]. Interestingly, treatment resistant epilepsy is also a constant finding in ring chromosome 20 syndrome, in patients with and without detectable deletions, and regardless of the size of the deleted segment [Zou et al, 2006].…”

“…A third hypothesis proposes that the epilepsy and other features of the ring 14 syndrome may be caused by the ring configuration, rather than by the loss of chromosomal material. In this case, there would be a silencing of 14q genes due to a telomere position effect or a spread of the heterochromatin-inactivated state of the centromere and shortarm (14p) DNA to the adjacent long arm (14q) [Schlade-Bartusiak et al, 2005;Ville et al, 2009;Zollino et al, 2009]. van Karnebeek et al [2002] suggest that only seizures can be explained by mitotic ring instability, while both seizures and retinitis pigmentosa can be explained by silencing of genes.…”