UNASSIGNED:评估丹麦Aicardi-Goutières综合征(AGS)和钾钠激活通道亚家族T成员1(KCNT1)相关癫痫的发生率,并描述诊断为AGS和KCNT1相关癫痫的患者的特征。
未经证实:AGS和KCNT1相关的癫痫是两种不同的罕见遗传性疾病。由于AGS和KCNT1相关癫痫的罕见,流行病学尚不清楚.这些疾病或具有疾病相关遗传变异的携带者的发病率仍然未知。
未经评估:这是一个回顾展,非干预性,基于人群的研究使用来自丹麦人口登记册的汇总数据和丹麦基于医院的患者水平数据,以确定2010年1月至2020年12月期间患有遗传确认的AGS和2012年1月至2020年12月期间KCNT1相关癫痫的患者.这些疾病的病例是从医院数据库中确定的,和致病性变体通过Sanger和/或全外显子组(基于小组)测序进行鉴定和确认。在单独的统计分析中估计AGS和KCNT1相关癫痫的发病率。
未经批准:共确定了7例AGS患者。AGS诊断时的平均年龄为19.4个月(中位年龄14个月)。据报道,TREX1(n<5)和RNASEH2B(n≥5)基因具有已确认的致病性变异。AGS的出生率为每100,000活产<0.7600。在总人口<18岁(n=7)中,年平均发病率为每100,000人每年0.0539(95%CI:0.0217-0.1111);在人口<12个月中,年平均发病率为每100,000人每年<0.7538(n<5),≥12个月和<18岁人群的年平均发病率为每100,000人每年<0.0406(n<5)。在研究期间共发现14例KCNT1相关癫痫病例(2016年n=5,2013年和2015年其余9例)。KCNT1病例诊断时的平均年龄为20.6岁(中位数19岁)。共有8例(57.1%)≥18岁,6例(42.9%)在诊断时<18岁。表型常染色体显性或散发性睡眠相关的运动过度癫痫(ADSHE)(n=10,71.4%)的报道最多;其余4例患有婴儿期癫痫伴移行性局灶性癫痫发作(EIMFS)或无法分类的发育性和癫痫性脑病(DEE)。KCNT1相关癫痫的出生发病率为每100,000例活产中≤1.1205。在研究期间,每100,000人每年的平均年发病率为0.0431(95%置信区间[CI]:0.0236-0.0723;n=14),在<18岁的人群中,0.0568(95%CI:0.0209-0.1237;n=6),在≥18岁和≤50岁的人群中,和0.0365(95%CI:0.0157-0.0718;n=8)。有3个家庭至少有2例诊断为KCNT1相关癫痫(平均每个家庭3.3例),表明3个家庭中总共有10个病例。所有ADSHE表型的KCNT1病例均来自3个家族。与以前的KCNT1研究相比,老年人和ADSHE病例的发生率更高,这可能是由于捕获了流行和家族以前未诊断的病例。不包括这些家庭案件,2012-2020年≤50岁人群的年平均发病率为每100,000人每年0.0123(95%CI:0.0034-0.0315,n=4).
UNASSIGNED:AGS和KCNT1相关的癫痫是特别罕见的疾病。在<18岁的人口中,AGS的年平均发病率为每100,000人中每年0.0539人,2010-2020年期间,出生率为每100,000活产中<0.7600人。2012-2020年,KCNT1相关癫痫的年平均发病率为每100,000人每年0.0431例,出生发病率为每100,000例活产婴儿1.1205例。鉴于类似的医疗保健系统和遗传池,这些发现可能为了解这些罕见疾病在北欧的发病率提供了见解.
UNASSIGNED: To estimate the incidence of Aicardi-Goutières syndrome (AGS) and potassium sodium-activated channel subfamily T member 1 (KCNT1)-related epilepsy in Denmark and to characterize the patients diagnosed with AGS and KCNT1-related epilepsy.
UNASSIGNED: AGS and KCNT1-related epilepsy are 2 distinct rare genetic disorders. Due to the rarity of AGS and KCNT1-related epilepsy, the epidemiology remains unclear. The incidences for these diseases or the carriers with disease-related genetic variants remain unknown.
UNASSIGNED: This is a retrospective, non-interventional, population-based study using aggregate data from the Danish population register and hospital-based patient-level data in Denmark to identify persons with genetically confirmed AGS between January 2010 to December 2020 and KCNT1-related epilepsies between January 2012 to December 2020. Cases of these disorders were identified from in-hospital databases, and pathogenic variants were identified and confirmed by Sanger and/or whole exome (panel-based) sequencing. The incidence of AGS and KCNT1-related epilepsy were estimated in separate statistical analyses.
UNASSIGNED: A total of 7 AGS patients were identified. The mean age at AGS diagnosis was 19.4 months (median age 14 months). TREX1 (n < 5) and RNASEH2B (n ≥ 5) genes were reported with confirmed pathogenic variants. The birth incidence of AGS was <0.7600 per 100,000 live births. The average annual incidence rate was calculated as 0.0539 (95% CI: 0.0217-0.1111) per 100,000 persons per year in the total population < 18 years (n = 7); the average annual incidence rate was <0.7538 per 100,000 persons per year (n < 5) in the population < 12 months, and the average annual incidence rate in the population ≥ 12 months and < 18 years was <0.0406 per 100,000 persons per year (n < 5). A total of 14 KCNT1-related epilepsy cases were identified during the study period (n = 5 in 2016, remaining 9 cases in 2013 and 2015). The mean age at diagnosis was 20.6 years (median 19 years) for KCNT1 cases. A total of 8 cases (57.1%) were ≥ 18 years, and 6 (42.9%) were < 18 years at diagnosis. The phenotype autosomal dominant or sporadic sleep-related hypermotor epilepsy (ADSHE) (n = 10, 71.4%) was most reported; the remaining 4 cases had either epilepsy of infancy with migrating focal seizures (EIMFS) or an unclassifiable developmental and epileptic encephalopathy (DEE). The birth incidence of KCNT1-related epilepsy was ≤1.1205 per 100,000 live births. The average annual incidence rates per 100,000 persons per year during the study period were 0.0431 (95% confidence interval [CI]: 0.0236-0.0723; n = 14) in the overall population ≤ 50 years, 0.0568 (95% CI: 0.0209-0.1237; n = 6) in the population < 18 years, and 0.0365 (95% CI: 0.0157-0.0718; n = 8) in the population ≥ 18 and ≤ 50 years. There were 3 families with at least 2 cases diagnosed with KCNT1-related epilepsies (on average 3.3 cases per family), indicating 10 cases in total within the 3 families. All KCNT1 cases of ADSHE phenotype came from the 3 families. The higher incidence of older ages and ADSHE cases compared with previous KCNT1 studies is likely due to the capture of prevalent and familial previously undiagnosed cases. Excluding these family cases, the average annual incidence was 0.0123 (95% CI: 0.0034-0.0315, n = 4) per 100,000 persons per year in the population ≤ 50 years during 2012-2020.
UNASSIGNED: AGS and KCNT1-related epilepsy are particularly rare diseases. The annual average incidence rate of AGS was 0.0539 per 100,000 persons per year in the population < 18 years and birth incidence was <0.7600 per 100,000 live births during 2010-2020. The average annual incidence rate of KCNT1-related epilepsy was 0.0431 per 100,000 persons per year in the population ≤ 50 years and the birth incidence was ≤1.1205 per 100,000 live births during 2012-2020. Given similar healthcare systems and genetic pools, these findings may provide insight on the incidence of these rare diseases in the Nordics.