Amnioinfusion Compared With No Intervention in Women With Second-Trimester Rupture of Membranes A Randomized Controlled Trial

OBJECTIVE: To assess the effectiveness of amnioinfusion in women with second-trimester preterm prelabor rupture of membranes. METHODS: We performed a nationwide, multicenter, open-label, randomized controlled trial, the PPROM: Expectant Management versus Induction of Labor-III (PPROMEXIL-III) trial, in women with singleton pregnancies and preterm prelabor rupture of membranes at 16 0/7 to 24 0/7 weeks of gestation with oligohydramnios (single deepest pocket less than 20 mm). Participants were allocated to transabdominal amnioinfusion or no intervention in a oneto- one ratio by a web-based system. If the single deepest pocket was less than 20 mm on follow-up visits, amnioinfusion was repeated weekly until 28 0/7 weeks of gestation. The primary outcome was perinatal mortality. We needed 56 women to show a reduction in perinatal mortality from 70% to 35% (b error 0.20, two-sided a error 0.05). RESULTS: Between June 15, 2012, and January 13, 2016, we randomized 28 women to amnioinfusion and 28 to no intervention. One woman was enrolled before the trial registration date (June 19, 2012). Perinatal mortality rates were 18 of 28 (64%) in the amnioinfusion group vs 21 of 28 (75%) in the no intervention group (relative risk 0.86, 95% CI 0.601.22, P5.39). CONCLUSION: In women with second-trimester preterm prelabor rupture of membranes and oligohydramnios, we found no reduction in perinatal mortality after amnioinfusion

De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

Background Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy. Methods Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible. Results All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X-inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles. Conclusions Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy

Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients

Many genes are candidates for involvement in epileptic encephalopathy (EE) because one or a few possibly pathogenic variants have been found in patients, but insufficient genetic or functional evidence exists for a definite annotation

Pitfalls in genetic testing: the story of missed SCN1A mutations

Peer reviewe

SARS-CoV-2 Antibodies in Adult Patients With Multiple Sclerosis in the Amsterdam MS Cohort

This cohort study assesses a group of patients with multiple sclerosis in Amsterdam, the Netherlands, for SARS-CoV-2 antibodies to quantify asymptomatic infections and immunological response to COVID-19

Prevalence of <i>SCN1A</i>-Related Dravet Syndrome among Children Reported with Seizures following Vaccination: A Population-Based Ten-Year Cohort Study

<div><p>Objectives</p><p>To determine the prevalence of Dravet syndrome, an epileptic encephalopathy caused by <i>SCN1A-</i>mutations, often with seizure onset after vaccination, among infants reported with seizures following vaccination. To determine differences in characteristics of reported seizures after vaccination in children with and without <i>SCN1A</i>-related Dravet syndrome.</p><p>Methods</p><p>Data were reviewed of 1,269 children with seizures following immunization in the first two years of life, reported to the safety surveillance system of the Dutch national immunization program between 1 January 1997 and 31 December 2006. Selective, prospective follow-up was performed of children with clinical characteristics compatible with a diagnosis of Dravet syndrome.</p><p>Results</p><p>In 21.9% (n = 279) of children, a diagnosis of Dravet syndrome could not be excluded based on available clinical data (median age at follow-up 16 months). Additional follow-up data were obtained in 83.9% (n = 234) of these children (median age 8.5 years).</p><p>15 (1.2% of 1,269; 95%CI:0.6 to 1.8%) children were diagnosed with <i>SCN1A</i>-related Dravet syndrome. Of all reported seizures following vaccinations in the first year of life, 2.5% (95%CI:1.3 to 3.6%) were due to <i>SCN1A</i>-related Dravet syndrome, as were 5.9% of reported seizures (95%CI:3.1 to 8.7%) after 2^nd or 3^rd DTP-IPV-Hib vaccination.</p><p>Seizures in children with <i>SCN1A</i>-related Dravet syndrome occurred more often with a body temperature below 38.5°C (57.9% vs. 32.6%, p = 0.020) and reoccurred more often after following vaccinations (26.7% vs. 4.0%, p = 0.003), than in children without a diagnosis of <i>SCN1A</i>-related Dravet Syndrome.</p><p>Conclusions</p><p>Although Dravet syndrome is a rare genetic epilepsy syndrome, 2.5% of reported seizures following vaccinations in the first year of life in our cohort occurred in children with this disorder. Knowledge on the specific characteristics of vaccination-related seizures in this syndrome might promote early diagnosis and indirectly, public faith in vaccination safety.</p></div

Baseline characteristics of children with seizures following vaccinations, and with or without <i>SCN1A</i>-related Dravet syndrome.

<p>Median age at first seizure was missing in 10 children. These were seizures unrelated and prior to, the reported vaccination.</p>*<p>4 children with first seizure after age 2.0 years, and at least 0.5 years after last vaccination.</p

Design of study.

<p>Design of study.</p

Characteristics of reported seizures following DTP-IPV(-)Hib vaccination in children with and without <i>SCN1A</i>-related Dravet syndrome.

*<p>P = 0.046 when the 69 missings were considered as temperature less than 38.5°C.</p