Analysis of clinical phenotype and SCN1A gene variant in a pedigree affected with genetic epilepsy with febrile seizures / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+).@*METHODS@#Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members.@*RESULTS@#The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%.@*CONCLUSION@#The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.

Early identification and diagnosis of epilepsy related to fever sensitivity / 中国当代儿科杂志

Febrile seizures are the most common nervous system disease in childhood, and most children have a good prognosis. However, some epilepsy cases are easily induced by fever and are characterized by "fever sensitivity", and it is difficult to differentiate such cases from febrile seizures. Epilepsy related to fever sensitivity includes hereditary epilepsy with febrile seizures plus, Dravet syndrome, and

A case of 16p13.11 microdeletion syndrome with febrile convulsion as the main manifestation / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a girl with febrile convulsion as the main manifestation.@*METHODS@#The child was subjected to whole exome sequencing (WES) and copy number variation sequencing(CNV-seq). Fluorescence quantitative PCR was carried out to validate the microdeletion in her family.@*RESULTS@#The 7-year-old girl was diagnosed with febrile convulsion (complex type) for having fever for 3 days, mild cough and low thermal convulsion once. Her father, mother and aunt also had a history of febrile convulsion. A heterozygous deletion with a size of approximately 1.5 Mb was detected in the 16p13.11 region by WES and CNV-seq. The deletion has derived from her father and was confirmed by fluorescence quantitative PCR.@*CONCLUSION@#16p13.11 microdeletion syndrome has significant clinical heterogeneity. Different from those with epilepsy, mental retardation, autism, multiple malformations, carriers of 16p13.11 deletion may only manifest with febrile convulsion. Deletion of certain gene(s) from the region may be related to febrile convulsion and underlay the symptom of this child.

Crisis febriles simples y complejas, epilepsia generalizada con crisis febriles plus, FIRES y nuevos síndromes / [Simple febrile seizure, complex seizure, generalized epilepsy with febrile seizure plus, FIRES and new syndromes].

Febrile seizures are the most common seizures in childhood. They have been observed in 2-5

of children before the age of 5, but in some populations this figure may increase to 15

. It is a common cause of pediatric hospital admissions and cause of anxiety for parents. Febrile seizures could be the first manifestation of epilepsy. About 13

of epileptic patients have a history of febrile seizure, and 30

have had recurrent febrile seizures. Their phenotypic characteristics allow, in the majority of cases, a classification of the seizure, an elaboration of a prognosis and to assume a specific therapeutic attitude. It is possible to describe a spectrum according to their severity, from the benign simple seizure to the more complex, febrile seizure plus, Dravet’syndrome, and FIRES. During the past decade, molecular genetic studies have contributed to the identification of genetic factors involved in febrile seizure and related disorders, making the necessity of a careful follow up of these patients in order to detect risk factors earlier. We have reviewed the medical literature to update current knowledge of febrile seizures, their prognosis and their relation to new epileptic syndromes.

Febrile seizures: Review article

Demographic, Genetic and clinical profiles Febrile seizures are broadly defined as seizures' occurring in the presence of fever, but in the absence of central nervous system infection. They occur in children aging from 6 months to 5 years with a mean age of onset of 18-24 months and they occur slightly more commonly in boys than in girls. 1 It is the most common reason for convulsions in children less than 6 years of age, and they occur in 2 to 5% of all children, although it has been reported to be more frequent in Asian countries. In Japan, the rate has been reported to be 7% and in Jordan 6.5%.2 It is thought that the rates in these areas are higher because some of the common infections of childhood may occur earlier in life when children are most susceptible to febrile seizures. 3 Febrile seizures can be divided into two types: simple and complex. Simple febrile seizures are characterized by the following: duration less than 15 minutes generally, and it occurs in normal children neurologically and developmentally. Complex febrile seizures have the following features: duration greater than 15 minutes, multiple within 24 hours, and/or focal. [2] The risk of recurrence after the first febrile seizure is about 33%. The risk factors for recurrence are: occurrence of the first febrile seizure at a young age; family history of febrile seizures; short duration of fever before the seizure; relatively low fever at the time of the initial seizure; and possibly a family history of an afebrile seizure. It has been observed that the time of recurrence is usually within the first year of onset. Although complex febrile seizures are not usually associated with an increased risk of recurrent febrile seizures, they may be a risk factor for epilepsy later in life. Febrile seizures seem to run in families, but their mode of inheritance is unknown. The risk for other siblings developing febrile seizures is about 10-20%, but may be higher if the parents also have a history of febrile seizures themselves. 4 In large families, the FS susceptibility trait is inherited by autosomal dominant pattern with a reduced penetrance. It has long been recognized that there is a significant genetic component for susceptibility to this type of seizure and this may be caused by a mutation in several genes.[2] In the presence of cases of FS and epilepsy in the same family one study the concept of a genetic epilepsy syndrome termed Generalized Epilepsy with FC plus [GEFS+]. GEFS has a spectrum of phenotypes including FC, and FC plus.[2]. Febrile seizures usually occur in the first 24 hours of the onset of fever. It has been suggested that it is the rapid rise in the child's temperature, which causes a febrile seizure rather than the actual height of the fever itself; however, there is no substantial proof to support this suggestion. The seizures are usually generalized and tonic-clonic, but other types may be present as well. There may be variations to this such as staring without stiffness, jerking movements without prior stiffening, and localized stiffness or jerking

Sydney crease in children with febrile seizures

Introducción. En el presente estudio se compararon las características clínicas y algunas variables previamente consideradas como factores de riesgo en niños con convulsiones febriles (CF) con y sin línea Sydney (LS); además se determinó la variación de los pliegues de flexión palmares en sus padres. Material y métodos. Noventa y un niños con un evento de CF se incluyeron en un estudio de corte transversal. Las características clínicas de las CF y algunos factores de riesgo para la recurrencia de CF o convulsiones no febriles fueron comparados en relación a la presencia (n= 43) o ausencia (n= 48) de LS. Además, se evaluaron los pliegues de flexión palmares en 85 de sus madres y 39 de sus padres. Resultados. Las características clínicas y las variables estudiadas fueron similares en los niños con y sin LS, con excepción de una menor frecuencia de infecciones respiratorias superiores como causa de la fiebre en los niños con CF y LS (P= < 0.05). Los padres de los niños con CF y LS mostraron mayor frecuencia estadística de LS (P= < 0.01), al compararlos con los padres de niños con CF sin LS, con razón de momios= 21.11 (intervalo de confianza al 95 por ciento 2.20 a 962.79). Conclusiones. Las características clínicas de las CF no se modificaron sustancialmente por la presencia o ausencia de LS. No se demostró asociación entre los factores de riesgo explorados y la presencia de LS. La transmisión paterna observada de la LS en la asociación CF/LS, sugiere la presencia de factores genéticos en la embriogénesis de los pliegues palmares y las CF.

Febrile convulsions in children

The term febrile convulsion is not a diagnostic entity. It simply describes any seizure that occurs in response to a febrile stimulus. It usually occurs between the age of 3 months and 5 years and occurs in 2-4% of young children. The typical febrile convulsion is a generalized tonic clonic seizure lasting between a few seconds and 15 minutes, followed by a period of drowsiness. Febrile seizures tend to occur in families, although the exact mode of inheritance is not known. Viruses are the most common cause of illness in children admitted to the hospital with a first febrile seizure. Routine laboratory studies are not indicated for patients who have febrile seizures and should be performed only as part of the evaluation for a source of fever. Prognosis is generally good. Only a small minority of children develop epilepsy or recurrent non-febrile seizures. Children with febrile seizures are at no greater risk of intellectual impairments than their peers. Treatment to prevent recurrence has not been shown to prevent later development of epilepsy

Dermatoglifos palmares en niños con convulsiones febriles / Palmodigital dermatoglyphic phenotypes in children with febrile convulsions

Se estudiaron los dermmatoglifos palmares de 30 niños con convulsiones febriles y sus controles, pareadas para edad, sexo y origen étnico. El grupo problema incluyó 19 niños y 11 niñas con convulsiones febriles no complicadas, con edad promedio 3.3 ñ 1.1 años. Ningún paciente tuvo historia de más de cuatro episodios; en 15 de ellos la crisis ocurrió por primera vez. Nueve niños (30 por ciento) tuvieron una historia familiar positiva para trastornos convulsivos. En ambos grupos, casos controles, se compararon los promedios y las frecuencias de 84 variables dermatoglíficas palmodigitales considerando por separado el sexo y la lateralidad. Sólo la presencia de la línea Sydney bilateral, mostró una frecuencia estadísticamente mayor en los niños con convulsiones febriles de 11/30 (36.6 por ciento) vs 3/30 (10 por ciento) en el grupo control (p<0.05). El resto de las variables no mostro diferencias entre ambos grupos. Se comenta el hecho de que un estudio previo mostró una mayor frecuencia de la línea simiana en los niños con convulsiones febriles; este hallazgo parece guardar relación con las evidencias del presente estudio, las que pueden ser resultado de la expresividad variable o pleiotropismo de una misma influencia genética. El encontrar este pliegue único de flexión palmar en niños con convulsiones febriles aporta información acerca de la heredabilidad o susceptibilidad genética para este problema.

Pontas parietais evocadas ao eletrencefalograma e convulsöes febris / Evoked parietal spikes in the electroencephalogram and febrile convulsions

Foi feita a pesquisa de pontas evocadas ao eletrencefalograma pela percussäo dos pés e mäos em 2307 crianças de 2 a 15 anos de idade. Foram encontradas pontas evocadas em 69 (2,99%). Convulsöes febris ocorreram em 226 casos e dentre esses 13 apresentaram pontas evocadas. Foi verificada associaçäo de convulsöes febris e pontas evocadas particularmente naquelas crianças em que havia atividade epileptiforme, principalmente de localizaçäo parietal. Säo feitos comentários sobre a importância desses achados em relaçäo à compreensäo da natureza da atividade epileptiforme em crianças com convulsöes febris, assim como em relaçäo às possíveis implicaçöes prognósticas