SCN2A and Its Related Epileptic Phenotypes

Epilepsies due to SCN2A mutations can present with a broad range of phenotypes that are still not fully understood. Clinical characteristics of SNC2A-related epilepsy may vary from neonatal benign epilepsy to early-onset epileptic encephalopathy, including Ohtahara syndrome and West syndrome, and epileptic encephalopathies occurring at later ages (usually within the first 10 years of life). Some patient may present with intellectual disability and/or autism or movement disorders and without epilepsy. The heterogeneity of the phenotypes associated to such genetic mutations does not always allow the clinician to address his suspect on this gene. For this reason, diagnosis is usually made after a multiple gene panel examination through next generation sequencing (NGS) or after whole exome sequencing (WES) or whole genome sequencing (WGS). Subsequently, confirmation by Sanger sequencing can be obtained. Mutations in SCN2A are inherited as an autosomal dominant trait. Most individuals diagnosed with SCN2A–benign familial neonatal-infantile seizures (BFNIS) have an affected parent; however, hypothetically, a child may present SCN2A-BNFNIS as the result of a de novo pathogenic variant. Almost all individuals with SCN2A and severe epileptic encephalopathies have a de novo pathogenic variant. SNC2A-related epilepsies have not shown a clear genotype–phenotype correlation; in some cases, a same variant may lead to different presentations even within the same family and this could be due to other genetic factors or to environmental causes. There is no “standardized” treatment for SCN2A-related epilepsy, as it varies in relation to the clinical presentation and the phenotype of the patient, according to its own gene mutation. Treatment is based mainly on antiepileptic drugs, which include classic wide-spectrum drugs, such as valproic acid, levetiracetam, and lamotrigine. However, specific agents, which act directly modulating the sodium channels activity (phenytoin, carbamazepine, oxcarbamazepine, lamotrigine, and zonisamide), have shown positive result, as other sodium channel blockers (lidocaine and mexiletine) or even other drugs with different targets (phenobarbital).

Monogenic causes in the Type 1 Diabetes Genetics Consortium cohort; low genetic risk for autoimmunity in case selection

Hypothesis About 1% of patients clinically diagnosed as type 1 diabetes have non-autoimmune monogenic diabetes. The distinction has important therapeutic implications but, given the low prevalence and high cost of testing, selecting patients to test is important. We tested the hypothesis that low genetic risk for type 1 diabetes can substantially contribute to this selection. Methods As proof of principle, we examined by exome sequencing families with two or more children, recruited by the Type 1 Diabetes Genetics Consortium and selected for negativity for two autoantibodies and absence of risk HLA haplotypes. Results We examined 46 families that met the criteria. Of the 17 with an affected parent, seven (41.2%) had actionable monogenic variants. Of 29 families with no affected parent, 14 (48.3%) had such variants, including five with recessive pathogenic variants of WFS1 but no report of other features of Wolfram syndrome. Our approach diagnosed 55.8% of the estimated number of monogenic families in the entire T1DGC cohort, by sequencing only 11.1% of the autoantibody-negative ones. Conclusions Our findings justify proceeding to large-scale prospective screening studies using markers of autoimmunity, even in the absence of an affected parent. We also confirm that non-syndromic WFS1 variants are common among cases of monogenic diabetes misdiagnosed as type 1 diabetes.

Effects of language dominance on home reading practices of bilingual families

Aims and objectives: Many children grow up in bilingual families; however, little is known about how these families use their two languages in their home reading practices. The goal of this study was to examine the effect of language proficiency on the shared storybook reading practices of bilingual families. Methodology: We gathered questionnaire data about home reading activities in French–English bilingual families with 5-year-old children ( n = 66) who had different proficiency levels in each language. Data and analyses: We compared home reading environment, parent reading practices, and child learning and interest in books across the families’ dominant and non-dominant languages using a series of 2-way mixed analyses of variance. Findings: Families gave more emphasis to reading practices in the family’s dominant language: they owned more books, read more often, spent more time, and started reading to the child at an earlier age in the dominant than in the non-dominant language. Dominance also affected parent reading behaviors: parents reported more often translating words and switching from their non-dominant to their dominant language. Parents reported that children enjoyed being read to and readily learned new words in both languages, but ratings were higher for the dominant language. Effects of dominance were strongest in families with less balanced language dominance. Originality: This study compares bilingual families’ home reading practices in both of their languages, providing a clearer picture of how families navigate early dual-language literacy in a bilingual community where both languages are spoken in everyday life and have similar sociolinguistic status. Significance: Results suggest that even in bilingual communities, family home reading practices may exacerbate uneven development across children’s two languages. These findings highlight the importance of identifying strategies to support enriched home reading practices in bilingual families’ non-dominant language.

Effects of language dominance on home reading practices of bilingual families

Aims and objectives: Many children grow up in bilingual families; however, little is known about how these families use their two languages in their home reading practices. The goal of this study was to examine the effect of language proficiency on the shared storybook reading practices of bilingual families. Methodology: We gathered questionnaire data about home reading activities in French–English bilingual families with 5-year-old children (N = 66) who had different proficiency levels in each language. Data and analyses: We compared home reading environment, parent reading practices, and child learning and interest in books across the families’ dominant and non-dominant languages using a series of 2-way mixed ANOVAs. Findings: Families gave more emphasis to reading practices in the family’s dominant language: they owned more books, read more often, spent more time, and started reading to the child at an earlier age in the dominant than in the non-dominant language. Dominance also affected parent reading behaviors: parents reported more often translating words and switching from their non-dominant to their dominant language. Parents reported that children enjoyed being read to and readily learned new words in both languages, but ratings were higher for the dominant language. Effects of dominance were strongest in families with less balanced language dominance. Originality: This study compares bilingual families’ home reading practices in both of their languages, providing a clearer picture of how families navigate early dual-language literacy in a bilingual community where both languages are spoken in everyday life and have similar sociolinguistic status.Significance: Results suggest that even in bilingual communities, family home reading practices may exacerbate uneven development across children’s two languages. These findings highlight the importance of identifying strategies to support enriched home reading practices in bilingual families’ non-dominant language.

P0034IDENTIFICATION OF FACTORS ASSOCIATED WITH PROGRESSION, PROGNOSIS AND TOLVAPTAN INDICATION IN POLYCYSTIC KIDNEY DISEASE PATIENTS

Background and Aims The identification of possible risk factors for the progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an emerging field especially after the introduction of the first disease-specific treatment. The present study aims to explore the associations between epidemiological, clinical and imagining data in a large cohort of ADPKD patients. Method This study was from a single outpatient clinic following patients with ADPKD. Patients were included in the study if they had a recent Magnetic Resonance Imaging (MRI) for measurement of Total Kidney Volume (TKV), a validated biomarker for disease progression. For all patients, the Mayo Clinic Imagining Category (MCIC) and the respective prediction for End Stage Renal Disease (ESRD) were calculated. Patients eligible for tolvaptan treatment (MCIC 1C, 1D, 1E, age < 55 years old and estimated-glomerular filtration rate (e-GFR) ≥ 25 ml/min) were identified. Characteristics including individual medical history, clinical and laboratory data were examined for possible associations with renal and imagining parameters using linear regression models. Results A total of 158 patients were included. Based on measurements of height-adjusted TKV (ht-TKV) and age, 5% of the patients were classified as 1A, 20% as 1B, 34% as 1C, 25% as 1D and 16% as 1E, MCIC. In multivariable analysis, patient’s age (p = 0.01), male sex (p < 0.001), parent’s age at which ESRD was reached (adjusted for patient age) (p < 0.001) and proteinuria (p = 0.04) were associated with ht-TKV. Parent’s age at ESRD differed significantly between the MCICs of the offspring (mean±(SD)), 70.83 (12.90) in 1A, 63.79 (11.39) in 1B, 57.32 (10.42) in 1C, 51.42 (9.18) in 1D and 47.94 (5.73) years old in 1E, (p < 0.001). Similarly, there were significant differences in the presence and the age of hypertension onset (p =0.004 and p = 0.003, respectively). In 104 patients (50 females, 54 males) who were eligible for tolvaptan treatment age at ADPKD diagnosis, age at hypertension onset and parent’s age reaching at ESRD were all significantly lower (p < 0.001 for all) when compared to non-eligible patients. Finally, factors associated with the prediction score of ESRD (e-GFR 10/ml/min) were hypertension, uric acid and the age at ESRD of the affected parent (p = 0.001, 0.02 and 0.01, respectively). Conclusion The age at which an affected parent had reached ESRD, as heritability estimator, was significantly associated with a worst phenotype, prognosis and tolvaptan indication. Early diagnosis of the disease, hypertension and its early onset, proteinuria and male sex are also possible risk factors for the progression of ADPKD.

Intervensi keperawatan terhadap self efficacy keluarga pasien skizofrenia

Keluarga merupakan orang-orang yang terkena dampak langsung dari anggota keluarga penderita skizofrenia. Keluarga juga pihak yang menderita seperti halnya penderita skizofrenia, bahkan skizofrenia merupakan gangguan yang dapat berlangsung seumur hidup, menjadi beban finansial dan emosional yang berat serta berkepanjangan bagi keluarga. Keluarga menanggung beban stigma yang cenderung melekat kepada keluarga yang mempunyai anggota keluarga penderita skizofrenia. Keluarga dalam merawat penderita skizofrenia membutuhkan self efficacy. Intervensi keperawatan diperlukan untuk meningkatkan self efficacy keluarga, memperkuat strategi koping, mencegah kekambuhan skizofrenia, meningkatkan fungsi keluarga dan menurunkan beban keluarga. Literatur review ini bertujuan mengetahui intervensi- intervensi yang digunakan terhadap self efficacy keluarga dengan skizofrenia. Metode yang digunakan menggunakan review artikel dan Jurnal keperawatan dari tahun 2007 sampai dengan tahun 2018. Hasil berbagai intervensi yang dilakukan menunjukkan perubahan yang bermakna terhadap self efficacy.Simpulan perawat perlu mengetahui berbagai intervensi keperawatan terhadap self efficacy keluarga untuk meningkatkan kemampuan keluarga dalam merawat dan penerimaan terhadap penderita dengan skizofrenia. Saran perlu dikembangkan intervensi keperawatan untuk lebih meningkatkan selft efficacy keluarga antara lain intervensi keperawatan Mindfulness Spiritual Islam. Kata Kunci : intervensi keperawatan, self effycacy, keluarga skizofrenia NURSING INTERVENTION OF FAMILY SELF EFFICACY SKIZOFRENIA PATIENTS ABSTRACTThe family is an affected parent directly from a family member with schizophrenia. Families also suffer from schizophrenia, even schizophrenia is a disorder that can last a lifetime, a heavy and prolonged financial and emotional burden on the family.Families bear the burden of stigma that tends to cling to families that have family members with schizophrenia.Families in treating schizophrenia need self efficacy. Nursing interventions are needed to improve family self-efficacy, strengthen coping strategies, prevent schizophrenia recurrence, improve family function and reduce family burden. This literature review aims to find out which interventions are used against family self-efficacy with schizophrenia. The method used uses a review of articles and nursing journals from 2007 to 2018. The results of various interventions conducted showed significant changes to self efficacy. Conclusions nurses need to know a variety of nursing interventions to family self efficacy to improve the ability of families to care for and receive patients with schizophrenia. Suggestions need to be developed nursing interventions to further improve the family efficacy, including Islamic Spiritual Mindfulness nursing interventions. Keywords: nursing interventions, self effycacy, schizophrenia family

Sibling competition in Blue Tits (Cyanistes caeruleus) is stronger in homozygous broods

Heterozygosity affects mate selection and can modulate interactions among family members and their fitness-related decisions. We studied whether nestling heterozygosity affected parent–offspring interactions and sib–sib competition in the Blue Tit (Cyanistes caeruleus) while controlling for the degree of relatedness among nestlings. Demanding environmental conditions might make the detection of heterozygosity-fitness correlations easier. Thus, we also investigated whether the decision rules of family members according to offspring heterozygosity were affected by brood size, as a proxy of the strength of sibling conflict. We found that chick individual heterozygosity was positively although weakly associated with individual body mass. Mean brood heterozygosity did not predict fledging success, but broods that fledged more chicks showed a higher number of less common alleles. Interestingly, fathers, but not mothers, favored heterozygous broods with many nestlings, that is, heterozygous broods with higher potential for sibling conflict. Moreover, the lower the mean brood heterozygosity the stronger the begging intensity when parents were absent, regardless of brood size. Finally, the degree of relatedness among nestlings was not associated with any behavioral parameter, supporting a more prominent role for heterozygosity in shaping intra-family interactions. Our findings suggest that offspring heterozygosity determines sex-specific rules of parental care and that genetic diversity is associated with lower sibling competition.

Schizophrenia risk conferred by protein-coding de novo mutations

Protein-coding de novo mutations (DNMs) in the form of single nucleotide changes and short insertions/deletions are significant genetic risk factors for autism, intellectual disability, developmental delay, and epileptic encephalopathy. In contrast, the burden of DNMs has thus far only had a modest documented impact on schizophrenia (SCZ) risk. Here, we analyze whole-exome sequence from 1,695 SCZ affected parent-offspring trios from Taiwan along with DNMs from 1,077 published SCZ trios to better understand the contribution of coding DNMs to SCZ risk. Among 2,772 SCZ affected probands, the increased burden of DNMs is modest. Gene set analyses show that the modest increase in risk from DNMs in SCZ probands is concentrated in genes that are either highly brain expressed, under strong evolutionary constraint, and/or overlap with genes identified as DNM risk factors in other neurodevelopmental disorders. No single gene meets the criteria for genome-wide significance, but we identify 16 genes that are recurrently hit by a protein-truncating DNM, which is a 3.15-fold higher rate than mutation model expectation of 5.1 genes (permuted 95% CI=1-10 genes, permuted p=3e-5). Overall, DNMs explain only a small fraction of SCZ risk, and this risk is polygenic in nature suggesting that coding variation across many different genes will be a risk factor for SCZ in the population.