6q Terminal Deletion Syndrome Associated with a Distinctive EEG and Clinical Pattern: A Report of Five Cases

Abstract

Summary:Purpose: Mental retardation, facial dysmorphisms, and neurologic and brain abnormalities are features of 6q terminal deletions. Epilepsy is frequently associated with this chromosome abnormality, but electroclinical findings are not well delineated. We report five unrelated patients with 6q terminal deletions and a peculiar clinical, EEG, and neuroradiologic picture of epilepsy, mental retardation, and colpocephaly.Methods: These three male and two female patients underwent general and neurologic examinations, repeated awake and sleep EEGs, and brain magnetic resonance imaging (MRI). A cytogenetic study and fluorescent in situ hybridization (FISH) with chromosome-specific subtelomeric probes were carried out in all cases.Results: All subjects had seizures characterized by vomiting, cyanosis, and head and eye version, with and without loss of consciousness. In four cases, EEGs showed posterior spike-andwave complexes, which were activated by sleep. No patient had status epilepticus or prolonged seizures. Brain MRI revealed colpocephaly and dysgenesis of the corpus callosum and brainstem in four patients; three of them also had hypertrophic massa intermedia. FISH analysis revealed a 6q terminal deletion in all patients, which ranged between 9 Mb (cases 2 and 3) and 16 Mb (case 4).Conclusions: We suggest that epilepsy associated with 6q terminal deletions is a new entity. Patients with dysmorphic features associated with focal occipital epilepsy, colpocephaly, and dysgenesis of the corpus callosum, thalami, and brainstem should be considered candidates for testing for 6q subtelomere deletions.

Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27

“…[1][2][3][4][5][6][7][8][9]15,16 Though the clinical phenotypes associated with this deletion are quite variable, reports in unrelated subjects from independent investigators have shown that ACC, PNH, polymicrogyria, hydrocephalus, and cerebellar malformations are the consistently observed features. A recent analysis of a comprehensive map of loci for ACC from 374 patients revealed that chromosome 6q27 was one of the few loci wherein six or more subjects with ACC have been reported.…”

“…Structural brain malformations are consistently observed in these patients and include agenesis of the corpus callosum (ACC), periventricular nodular heterotopia (PNH), polymicrogyria, hydrocephalus, and cerebellar malformations. [1][2][3][4][5][6][7][8][9][10] Whereas previous studies have attempted to delineate the critical region responsible for brain malformations in patients with terminal 6q27 deletions, the sensitivity of the methodologies used has prevented the fine-mapping of the critical region. 1,6 A detailed genomic analysis of the subtelomeric chromosome 6q region would help identify the putative genes involved in the causation of brain malformations.…”

Structural genomic variation in childhood epilepsies with complex phenotypes

“…Both deletions were the two largest deletions in our sample, exceeding 10 Mb. Epilepsy in 6q terminal deletion syndrome is a welldescribed feature, 16,17 whereas intellectual disability is usually the most prominent feature in 3p deletion syndrome. 18,19 As parents were not available for a significant proportion of patients, the frequency of de novo variants might be an underestimation.…”

Ring 14 chromosome presenting as early‐onset isolated partial epilepsy

“…22 Patterns of occipital seizures suggestive of Panayiotopoulos syndrome have been reported in cases of 6q-ter microdeletion. 23 Thus, karyotyping should be included in the screening of children with early-onset partial epilepsy for whom no lesion is identified on MRI. Another remarkable point is the difference in phenotype between our cases and classic ring 14 syndrome.…”

“…Several hypotheses have been put forward to account for the clinical manifestations learning disability, epilepsy, growth retardation) in ring chromosome syndromes: 23 the presence of a susceptibility gene on the q arm, which is deleted during ring formation; a telomere position effect, silencing the genes on the q arm juxtaposed near the p arm telomere; and the silencing of genes as a result of the spreading of the inactivated heterochromatin state of the DNA of the p arm to the adjacent q arm. In ring 14 syndrome, the telomeric region of the long arm was thought to be a region of interest, because some cases with telomeric 14q deletion have characteristics also seen in cases of ring 14 syndrome.…”