Early onset myoclonic epilepsy and 15q26 microdeletion: Observation of the first case

Abstract

SUMMARYThe authors report the study of a 30-month-old girl with refractory myoclonic epilepsy associated with mental retardation, growth delay, peculiar facial appearance, and minor physical anomalies. Extensive genetic studies were performed, including an array-based comparative genomic hybridization (array-CGH) that showed a cryptic interstitial deletion of 15q (5 Mb) affecting the 15q26.1-26.2 region. Partial deletions of the long arm of chromosome 15, including the 15q26 region, were observed in syndromic associations that typically include congenital diaphragmatic hernia, but neurologic features were poorly described and epileptic seizures were never reported. Our findings suggest that genes for seizures could be included in the 15q26.1q26.2 deletion interval.

CHD2 mutations are a rare cause of generalized epilepsy with myoclonic–atonic seizures

“…The epileptic phenotype was classified as MAE in 3 cases [5,6], LGS in 3 cases [5,6,8,9], DS in 3 cases [9], and Jeavons syndrome in 1 case [15]. Eleven cases had other unspecified generalized epilepsies [5,6,[11][12][13][14][15][16]. Among our series of 20 patients with MAE, only one of them had a CHD2 gene mutation.…”

“…Epilepsy & Behavior 51 (2015) 53-56 Moreover, autistic behavior and facial dimorphisms have been reported in cases with gene deletion [11,12,[14][15][16]. The aim of this study was to assess the impact of CHD2 mutations in a series of patients with MAE.…”

CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures

“…An earlier onset of seizures at 6 months was noted in the single case with a de novo splice site mutation from the EPI4K study. 11 A de novo CHD2 mutation has also been reported in a child with intellectual disability and absence epilepsy (T604Lfs* 19) 12 and another case with ASD alone (D856G). 13 Case 9 had a chromosome 15q26 microdeletion that results in partial deletion of CHD2.…”

“…Intellectual disability was mild to severe. 11,[14][15][16][17] The missense, nonsense, frameshift, and splice site mutations in CHD2 encephalopathy do not cluster in any definite pattern within the gene (figure 4), and the location or type of mutation does not correlate with disease severity. CHD2 is among the genes that are most intolerant to functional variation (ranked in top 2.5%).…”

A Novel Genetic Syndrome Caused by Haploinsufficiency of CHD2, a Regulator of Chromatin Structure

“…Alignment of all patients' deletions reveals that CHD2 deletions, with or without deletion of RGMA, may produce seizures indicating that deletion of RGMA is not required for manifestation of this phenotype. Larger and more complex deletions involving CHD2 have also been identified (reported deletions sizes were 3.3 Mb and 5 Mb, in addition to one patient with 6 copy number changes, including a 2 Mb chromosome 15q26.1 deletion) [7][8][9]. Although the clinical phenotypes are likely modified by the greater number of genes deleted in these patients, developmental delay, facial dysmorphia, and seizures were common features shared by these larger CHD2 deletion carriers.…”