SCN1A Variants as the Underlying Cause of Genetic Epilepsy with Febrile Seizures Plus in Two Multi-Generational Colombian Families.

Genetic epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant disorder with febrile or afebrile seizures that exhibits phenotypic variability. Only a few variants in SCN1A have been previously characterized for GEFS+, in Latin American populations where studies on the genetic and phenotypic spectrum of GEFS+ are scarce. We evaluated members in two multi-generational Colombian Paisa families whose affected members present with classic GEFS+. Exome and Sanger sequencing were used to detect the causal variants in these families. In each of these families, we identified variants in SCN1A causing GEFS+ with incomplete penetrance. In Family 047, we identified a heterozygous variant (c.3530C > G; p.(Pro1177Arg)) that segregates with GEFS+ in 15 affected individuals. In Family 167, we identified a previously unreported variant (c.725A > G; p.(Gln242Arg)) that segregates with the disease in a family with four affected members. Both variants are located in a cytoplasmic loop region in SCN1A and based on our findings the variants are classified as pathogenic and likely pathogenic, respectively. Our results expand the genotypic and phenotypic spectrum associated with SCN1A variants and will aid in improving molecular diagnostics and counseling in Latin American and other populations.

Protective association exhibited by a single nucleotide polymorphism of the IFIH1 gene in patients with psoriasis: A case-control study. / Asociación protectora del polimorfismo de nucleótido único en IFIH1 en pacientes con psoriasis: estudio de casos y controles.

INTRODUCTION: Psoriasis is a chronic inflammatory dermatosis, a with variable clinical presentation and whose multifactorial etiology carries an essential genetic component. Multiple genetic variations associated with psoriasis have been described around the world. However, these variants are unknown among the Colombian population. This study aimed to evaluate the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene and its ssociation with the development of psoriasis in a Colombian population. METHODS: An observational, unmatched, case-control study was performed, including 51 patients with psoriasis and 151 population controls, all with self-reported Paisa ancestry (from the Antioquia region). All individuals were genotyped for the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene, and its association with psoriasis was pursued. Both groups were demographically characterized, and cases were also assessed for clinical variables. RESULTS: Through the allelic association analysis, cases were found to have a lower frequency of the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene than controls; 5% versus 22.67%, respectively. There were no significant differences in age or sex. We also found that psoriasis vulgaris was the most common variant (78%), that about half of the cases had nail psoriasis (56%), 19.6% had psoriatic arthritis, and that 45% had some comorbidity. CONCLUSIONS: The results obtained from this study confirm that carriers of the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene have a decreased risk of developing psoriasis.

INTRODUCCIÓN: La psoriasis es una dermatosis inflamatoria crónica, con presentación clínica variable y cuya etiología involucra un componente genético importante. Alrededor del mundo se han descrito múltiples variaciones genéticas asociadas a la enfermedad. Sin embargo, en población colombiana se desconocen estas variantes. En este estudio se evalúa el polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 y su asociación con el desarrollo de psoriasis en población colombiana. Además, se caracteriza a los individuos demográfica y clínicamente. MÉTODOS: Se realizó un estudio observacional de casos y controles, no pareado, que incluyó 51 individuos con psoriasis y 151 controles poblacionales, todos de ancestría paisa (proveniente de la región de Antioquia) auto reportada. A todos los individuos se les realizó genotipificación del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 y se les determinó la asociación con la enfermedad. Se caracterizaron demográficamente ambos grupos y los casos clínicamente. RESULTADOS: Se encontró que los casos presentaron una menor frecuencia del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 en relación a los controles, 5 versus 22,67% respectivamente, con un análisis de asociación alélico. No hubo diferencias significativas en edad ni en sexo. La psoriasis vulgar fue la variante de presentación más común (78%). Alrededor de la mitad de los casos presentaron psoriasis ungular (56%), en menor frecuencia artritis psoriásica (19,6%) y el 45% de los casos tuvo alguna comorbilidad. CONCLUSIONES: Los resultados obtenidos confirman que los portadores del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1, presentan un riesgo disminuido de desarrollar psoriasis.

Differential Clinical Features in Colombian Patients With Rolandic Epilepsy and Suggestion of Unlikely Association With GRIN2A, RBFOX1, or RBFOX3 Gene Variants.

PURPOSE: Our purpose was to describe the phenotypic features and test for association of genes GRIN2A, RBFOX1 and RBFOX3 with rolandic epilepsy in patients from Colombia. METHODS: Thirty patients were enrolled. A structured interview was applied. In addition, saliva samples were collected from the patients and their parents. One polymorphism in each of GRIN2A, RBFOX1 and RBFOX3 genes was tested. RESULTS: The average age at onset was 5.3 years. Almost half the sample presented prolonged seizures (>5 minutes); although the majority of the patients presented their seizures only while asleep, over a quarter presented them only while awake. The most frequent comorbidity was the presence of symptoms compatible with attention-deficit hyperactivity disorder (ADHD). Personal history of febrile seizures and parasomnias were equally frequent (20%). Family history of any type of epilepsy was reported in 80% of the patients, followed by migraine (73.3%) and poor academic performance (63.3%). About half the sample reported sleepwalking in parents or sibs. Most patients had received pharmacologic treatment. We found no association of rolandic epilepsy with the single nucleotide polymorphisms tested. CONCLUSIONS: Our rolandic epilepsy cohort presents clinical features clearly different from other cohorts. For instance, age at onset is much earlier in our set of patients, and personal and family history of febrile seizures as well as parasomnias are highly prevalent in our sample. No association of rolandic epilepsy with variants at the 3 genes tested was found. This lack of association may reflect the high genetic heterogeneity of the epilepsies.

Sleepwalking and Sleep Paralysis: Prevalence in Colombian Families With Genetic Generalized Epilepsy.

BACKGROUND: Sleep deprivation commonly increases seizure frequency in patients with genetic generalized epilepsy, though it is unknown whether there is an increased prevalence of sleepwalking or sleep paralysis in genetic generalized epilepsy patients. Establishing this could provide insights into the bio-mechanisms or genetic architecture of both disorders. The aim of this study was to determine the prevalence of sleepwalking and sleep paralysis in a cohort of patients with genetic generalized epilepsy and their relatives in extended families. METHODS: A structured interview based on International League Against Epilepsy (ILAE) and International Classification of Sleep Disorders (ICSD-3) criteria was applied to 67 index cases and their relatives to determine genetic generalized epilepsy subtypes and assess the occurrence of sleepwalking or sleep paralysis. Bivariate analysis was performed using chi-square and Fisher exact tests. RESULTS: The prevalence of sleepwalking and sleep paralysis was 15.3% (95% confidence interval 12.1-18.9) and 11.7% (95% confidence interval 8.7-15.3), respectively. Unusually, no sleepwalkers were found among individuals displaying epilepsy with generalized tonic-clonic seizures. Approximately a quarter of the patients had either parasomnia or genetic generalized epilepsy. Over half the genetic generalized epilepsy families had at least 1 individual with sleepwalking, and more than 40% of the families had one individual with sleep paralysis. CONCLUSION: The prevalence of sleepwalking or sleep paralysis is reported for individuals with genetic generalized epilepsy and their relatives. The co-existence of either parasomnia in the genetic generalized epilepsy patients and the co-aggregation within their families let suggest that shared heritability and pathophysiological mechanisms exist between these disorders. We hypothesize that sleepwalking/sleep paralysis and genetic generalized epilepsy could be variable expression of genes in shared pathways.

Caracterización de la epilepsia benigna de la infancia con puntas centrotemporales. Estudio de corte transversal realizado en niños atendidos en dos laboratorios de referencia de la ciudad Medellín (2011-2016) / Characterization of childhood benign epilepsy with centrotemporal spikes. Cross-sectional study done in children seen in reference laboratories in the city of Medellin (2011-2016)

Introducción: La epilepsia benigna de la infancia con puntas centro-temporales es el síndrome epiléptico focal más común en pediatría. No hay datos sistematizados en Colombia sobre esta enfermedad. Objetivo: Describir las características clínicas, electroencefalográficas y familiares de este síndrome. Materiales y métodos: Estudio descriptivo, retrospectivo, de corte transversal, con análisis exploratorio. Se incluyeron pacientes <18 años que consultaron a 2 laboratorios de electroencefalografía (EEG) en Medellín, Colombia, de 2011 a 2016, que cumplieron criterios diagnósticos de epilepsia rolándica, con EEG que mostraba puntas centro-temporales con máxima negatividad en los electrodos centro-temporales (C3, C4 y T3,T4), con activación en sueño. Se calcularon las frecuencias y proporciones para variables cualitativas y promedios y desviaciones estándar (DE) para las cuantitativas. En el análisis exploratorio se utilizaron las pruebas de chi cuadrado, test exacto de Fisher y test Shapiro ­Wilk. Resultados: Se incluyeron 44 pacientes, 46% mujeres, 54% hombres. La edad promedio de inicio de la epilepsia fue 6,6 años (DE: 2,3). Las manifestaciones clínicas más frecuentes de esta epilepsia fueron: Sialorrea 27% y sonidos faríngeos 27%. Las crisis se presentaron durante el sueño en 43%, no muy diferente del porcentaje en vigilia, 46%. El 76% había presentado máximo 4 crisis. No hubo diferencias respecto a la lateralidad de la actividad epileptiforme en el EEG. La fase del sueño en la que más se presentó la actividad epileptiforme fue N2. En el 57%, la actividad se presentaba en salvas. Solo el 20% presentó actividad extra centro-temporal. El 32% de los pacientes tenía antecedente familiar de epilepsia. Las comorbilidades más frecuentes fueron bajo rendimiento escolar 34%, trastorno del lenguaje 25% y TDAH 23%. El 61% de los pacientes recibía tratamiento farmacológico y el medicamento más usado fue la carbamazepina en 25%. En el análisis exploratorio se encontró que la frecuencia de los complejos POL era más baja: 3,3 Hz, en los pacientes con trastorno del lenguaje que en los pacientes sin esta comorbilidad: 3,6 Hz, (p=0.02). Conclusión: Aunque el tamaño de la muestra de este estudio no es grande, tiene el valor de ser la primera descripción clínica, electroencefalográfica y familiar de la epilepsia rolándica en Colombia. Las características clínicas son similares a lo descrito en otras series, pero con mayor proporción de generalización de las crisis. La frecuencia en Hz de los complejos POL estuvo por encima de lo previamente informado. El antecedente familiar de epilepsia fue 3 veces más alto en los pacientes de este estudio, lo que podría sugerir que existen factores genéticos y/o ambientales comunes entre este síndrome y otros tipos de epilepsia en nuestra población. Las comorbilidades más frecuentes fueron bajo rendimiento escolar, TDAH y trastorno del lenguaje, los cuales se deben buscar activamente en estos pacientes. La frecuencia en Hz de los complejos POL podría ser un marcador de pronóstico respecto al lenguaje en pacientes con epilepsia rolándica.

Introduction: Benign epilepsy with centro-temporal spikes (BECTS) is the most frequent focal epileptic syndrome in childhood. There are no systematic data about it at Colombia. Our objective was to describe the clinical, electroencephalographic and familiar characteristics of this syndrome. Materials and methods: Retrospective, descriptive, cross- sectional study, with exploratory analysis. Patients admitted were children under 18 years of age, who had attended one of two selected electroencephalography laboratories at Medellín, Colombia, from 2011 to 2016, and filled diagnostic criteria for rolandic epilepsy, EEG with centro-temporal spikes, maximal electronegativity at C3, C4 and T3, T4 electrodes, and activation during sleep. Frequencies and proportions were calculated for qualitative variables, averages and standard deviation for quantitative variables. Chi square, Fisher test and Shapiro-Wilk test were used for exploratory analysis. Results: 44 patients were included, 46% women and 54% men. Average age when epilepsy started was 6.6 years old (SD: 2.3). Most frequent symptoms were: Hypersalivation and oropharyngeal sounds with 27% each. Seizures presented during sleep in 43% with a similar proportion during awake. 76% had presented 4 seizures top. There were no differences in the side of epileptiform activity in EEG. N2 was the sleep phase with more epileptiform activity. In 57% of cases the epileptiform activity presented in clusters. Only 20% had extra centrotemporal activity. There was familiar history of epilepsy in 32%. The most frequent comorbidities were poor school performance: 34%, speech disorder: 25% and ADHD: 23%. 61% of patients were on treatment, and the most frequent medication was carbamazepine: 25%. The exploratory analysis showed that the frequency of spike and slow wave complexes were slower: 3.3 Hz, in patients with speech disorder than in patients without it: 3.6 Hz (p=0.02). Conclusion: This is the first clinical, electroencephalographic and familiar description of rolandic epilepsy in our country. Clinical presentation was similar to other reports, but our patients had more generalization of seizures. The frequency of spike and slow wave complexes (Hz) were in general above of previous reports. Family history of epilepsy was three times higher in patients of this study, suggesting that there are some common genetic and environmental factors between this syndrome and other types of epilepsy in our population. The most frequent comorbidities were poor school performance, speech disorder, and ADHD. This should be carefully evaluated in patients with this syndrome. The frequency of spike and slow wave complexes (Hz) could be a marker of speech prognosis in patients with rolandic epilepsy.