Genetic and phenotypic spectrum of Chinese patients with epilepsy and photosensitivity

Abstract

ObjectiveTo determine the contribution of genetic etiologies in epilepsy with photosensitivity.MethodsA total of 35 epileptic patients with genetic photosensitivity from January 2019 to May 2021 were analyzed.ResultsPathogenic variants were identified in 35 patients, including SCN1A(7) CHD2(6), TPP1(3), SYNGAP1(3), GABRA1(2), GABRG2(1), KCTD7(1), MFSD8(1), KCNC1(1) GBA(1), CACNA1A(1), KCNMA1(1), FLNA(1), SZT2(1), SLC2A1(1), 5q33.2-34del(1), and mitochondrial variants(3). The predominant epileptic syndrome was progressive myoclonus epilepsy (PME) and Dravet syndrome, while the most common seizure type in both spontaneous seizures and photoconvulsive response (PCR) was myoclonic seizures. The abnormal EEG background and brain MRI were mainly seen in the PME patients. In PME, initial low-frequencies (1–6 Hz) photosensitivity was observed in 70% (7/10) of patients. Among the other patients, 12 patients (48.0%, 12/25) had photosensitivity at initial low -frequencies and 12 patients (48.0%, 12/25) had photosensitivity at initial middle frequencies (6–20 Hz). At the 1-year follow-up, 77.7% (21/27) still remained photosensitive.ConclusionThe most common genes for epilepsy with genetic photosensitivity are SCN1A and CHD2, and the most common syndromes are PME and Dravet syndrome. MFSD8, KCNMA1, SZT2, FLNA, and SLC2A1 variants might be candidate genes for photosensitivity. PPRs at initial low-frequencies may be a marker of PME, and the most typical feature of genetic photosensitivity may be low- or middle- frequencies induced PPRs. Photosensitivity in epilepsy with genetic photosensitivity may be difficult to disappear in a short period of time.

KCTD7‐related progressive myoclonic epilepsy: Report of 42 cases and review of literature

“…Notably, the PPR was documented at a variety of frequency ranges in the literature as well, including low flash frequencies in some cases (i.e., 1 Hz) and higher flash frequencies (i.e., 8-19 Hz) in others. 14,15,22,24,[31][32][33][34] Thus, not all cases with PME and biallelic KCTD7 variants present with a PPR at low flash frequency ranges. Furthermore, an occipital predominance of the PPR was also reported.…”

“…KCTD7 biallelic pathogenic variants are predominantly associated with early onset PME, and seizures are the initial symptom in most children (i.e., 60%-70%). 14,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Myoclonic seizures are the most frequent seizure type observed at disease onset, followed by generalized tonic-clonic, generalized clonic, generalized atonic, and generalized tonic seizures. Over time, nearly all children in our cohort and in the literature developed myoclonic seizures.…”

“…In addition, the age at symptom onset was similar between our cohort and the literature, occurring in the first year and a half of life. 14,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] However, in the literature disease onset could occur as late as 36 months. 15,24,27 Progressive neurological decline with or without stabilization following a period of normal development was observed in one third of our cohort.…”

“…14,15,24 The neuroimaging findings in this cohort and the literature included similar findings, such as cortical atrophy, cerebellar atrophy, whiter matter signal changes, and delayed myelination and/or hypomyelination. 14,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Moreover, in one child in the literature, focal cortical dysplasia was documented. 23 Initial brain MRI was normal in two thirds of our cohort versus one third of reported cases.…”

“…Forty-one records were retrieved and assessed for eligibility. Twenty-three studies were included, [14][15][16][17][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] and 18 studies were excluded 13,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] for the following reasons: variables of interest not reported, 13,[41][42][43][44][47][48][49][50][51]53,…”