STAG2 microduplication in a patient with eyelid myoclonia and absences and a review of EMA-related reported genes.

Xq25 microduplication involving exclusively STAG2 is a new distinctive cohesinopathy including mild to moderate intellectual disability, speech delay and facial dysmorphism. Seizures seem to be scarce, but detailed seizure type descriptions are missing. We report the case of an 8-year-old boy with mild intellectual disability and eyelid myoclonia with onset at age of 3 years, initially misinterpreted as tics. An ictal VIDEO-EEG documented eye closure elicited generalized 3 Hz spike-waves or polyspike-waves concomitant to eyelid myoclonia, sometimes associated to brief clinically observable absences. Intermittent photic stimulation revealed a photoparoxysmal response. Array CGH identified a 199 kb copy number gain in Xq25 including the whole STAG2 gene, inherited from his asymptomatic mother. To the best of our knowledge, this is the first case of STAG2 encephalopathy fulfilling all electroclinical criteria for epilepsy with eyelid myoclonia and absences (EMA), formally named Jeavons syndrome (JS). As for other Genetic Generalized Epilepsy syndromes, EMA/JS usually occurs in normally developing children. Intellectual disability of variable degree is occasionally reported. On the background of other genes responsible for Developmental and Epileptic Encephalopathies, linked to specific generalized seizure types or seizure combinations, we discuss the contribution of pathogenic variants in CHD2, SYNGAP1 and some other genes as, RORB, NEXMIF and KCNB1 to this peculiar EMA phenotype.

Whole-exome sequencing improves the diagnosis yield in sporadic infantile spasm syndrome.

Infantile spasms syndrome (ISs) is characterized by clinical spasms with ictal electrodecrement, usually occurring before the age of 1 year and frequently associated with cognitive impairment. Etiology is widely heterogeneous, the cause remaining elusive in 40% of patients. We searched for de novo mutations in 10 probands with ISs and their parents using whole-exome sequencing (WES). Patients had neither consanguinity nor family history of epilepsy. Common causes of ISs were excluded by brain magnetic resonance imaging (MRI), metabolic screening, array-comparative genomic hybridization (CGH) and testing for mutations in CDKL5, STXBP1, and for ARX duplications. We found a probably pathogenic mutation in four patients. Missense mutations in SCN2A (p.Leu1342Pro) and KCNQ2 (p.Ala306Thr) were found in two patients with no history of epilepsy before the onset of ISs. The p.Asn107Ser missense mutation of ALG13 had been previously reported in four females with ISs. The fourth mutation was an in-frame deletion (p.Phe110del) in NR2F1, a gene whose mutations cause intellectual disability, epilepsy, and optic atrophy. In addition, we found a possibly pathogenic variant in KIF3C that encodes a kinesin expressed during neural development. Our results confirm that WES improves significantly the diagnosis yield in patients with sporadic ISs.

Atypical hemispheric asymmetries for the processing of phonological features in children with rolandic epilepsy.

We assessed language lateralization in 177 healthy 4- to 11-year-old children and adults and atypical asymmetries associated with unilateral epileptic foci in 18 children with benign epilepsy with centrotemporal spikes (BECTS). Dichotic listening results revealed two indices of immature functional asymmetry when the focus was left-sided (BECTS-L). First, children with BECTS-L did not show left hemisphere dominance for the processing of place of articulation, which was recorded in children with BECTS-R and control children. On the contrary, healthy children exhibited a gradual increase in left hemisphere dominance for place processing during childhood, which is consistent with the shift from global to finer-grained acoustic analysis predicted by the Developmental Weighting Shift model. Second, children with BECTS-L showed atypical left hemisphere involvement in the processing of the voiced value (+V), associated with a long acoustic event in French stop consonants, whereas right hemisphere dominance increased with age for +V processing in healthy children. BECTS-L, therefore, interferes with the development of left hemisphere dominance for specific phonological mechanisms.

Hemispheric lateralization of cognitive functions in children with centrotemporal spikes.

We assessed the impact of unilateral epileptic foci in benign idiopathic partial epilepsy of childhood with rolandic discharges (BECT) on performance and hemispheric specialization in lateralized cognitive functions. Six children with BECT with a left-sided focus (BECT-L), 6 children with BECT with a right-sided focus (BECT-R), and 12 control children were tested in verbal, visual-spatial, and visual-attention tasks, with visual hemifield presentation. Children with BECT-R were impaired in the visual-spatial task relative to those with BECT-L, and the typical left-hemisphere (LH) advantage was not reported in the verbal task in children with BECT-L. Additionally, the classic global superiority effect was lacking in children with BECT-R, which may be due to impaired performance of the right hemisphere specialized in global (vs local)-level processing. These data argue for the deleterious effect of epileptic discharges per se on cognitive functions in the developing brain, and the decisive role of epileptic focus lateralization in specific cognitive impairments and hemispheric specialization.

Effect of sleep stages on synchronized spontaneous otoacoustic emissions in pre-term neonates.

OBJECTIVES: In infants, auditory tests are mainly performed during sleep, since they spend most of their time asleep, and because quiet is required for the duration of the recording session to obtain a precise and reliable response. The aim of this study was to investigate the effect of sleep stages on synchronized spontaneous otoacoustic emissions (sSOAEs) in pre-term neonates at the age where the sleep states begin to be well established and auditory screening can be performed in a neonatology unit before discharge. METHODS: Synchronized SOAEs were repeatedly recorded during a polygraphic sleep recording using the Otodynamic ILO88 system in 10 pre-term neonates at 36 weeks post-conception. RESULTS: Variations of sSOAE peak numbers occurred in each subject during the recording session. There was no clear relation between sSOAE peak number fluctuations and the different sleep stages. CONCLUSIONS: The sSOAE variations appeared to be closely related to experimental conditions, i.e. the mean background noise level. sSOAEs with the highest amplitude were always recorded; however, those with the smallest amplitude were the first to disappear from the recordings with higher background noise.