If the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes Nav1.1 protein, undergoes pathological mutation, it results in a wide range of epileptic syndrome, including febrile seizure, genetic epilepsy with febrile seizure plus (GEFS+), and developmental and epileptic encephalopathy (DEE), including Dravet syndrome. We present the case of a five-and-a-half-month-old boy with SCN1A gene-related epileptic seizures, starting as focal seizures and progressing to generalized tonic-clonic seizures. Despite treating the seizures with multiple antiepileptic drugs, including phenytoin, sodium valproate, levetiracetam, perampanel, and clobazam, it was very difficult to control the seizures, and genetic testing was suggested. The SCN1A mutation leads to either loss of function, including GEFS+ and Dravet syndrome, or gain of function, including familial hemiplegic migraine type 3. The case emphasizes the importance of genetic testing in refractory epilepsy management to provide medical strategies for the diagnosis. It focuses on the difficulties faced in diagnostic and treatment strategies for the management of SCN1A-related epilepsy. It emphasizes the importance of monitoring and personalized treatment strategies to reduce the incidence of refractory epilepsy.

The purpose of this study was to investigate the timing of generalized electroencephalographic abnormalities in patients with juvenile myoclonic epilepsy who were followed up long term before the onset of juvenile myoclonic epilepsy. We enrolled juvenile myoclonic epilepsy patients whose course of epilepsy had been observed for >5 years before the onset of juvenile myoclonic epilepsy, those who had undergone electroencephalogram recording more than twice before the onset of juvenile myoclonic epilepsy, and those who had terminated antiseizure medications for at least 2 years before the onset of juvenile myoclonic epilepsy. Patients who had transitioned from childhood absence epilepsy to juvenile myoclonic epilepsy were excluded. We retrospectively reviewed the medical records and neurophysiological data of the patients. Four patients met the inclusion criteria. One patient was diagnosed with febrile seizures during childhood, and the remaining three had transitioned to juvenile myoclonic epilepsy from other epileptic disorders, such as self-limited epilepsy with autonomic seizures, genetic epilepsy with febrile seizure plus, or nonspecific genetic generalized epilepsy. All patients exhibited generalized spike-wave discharges or photoparoxysmal responses for >2 years before the onset of juvenile myoclonic epilepsy. The four patients had transitioned to juvenile myoclonic epilepsy from other epileptological preconditions. Patients with juvenile myoclonic epilepsy may show generalized electroencephalographic abnormality many years prior to the onset of symptoms. Generalized spike-waves on the electroencephalogram during the course of any type of epilepsy or febrile seizure may be a risk factor for developing juvenile myoclonic epilepsy.

Febrile Seizures (FS) are the most common seizures in children younger than 5 years. In the last decade, various coding and noncoding sequence variations of voltage-gated sodium channels SCN2A have been identified in patients with seizures, implying their genetic base. We aimed to evaluate the association between SCN2A c. G/A genetic polymorphism among Egyptian children with febrile seizure plus. The present cross-sectional study was carried out on 100 epileptic infants and children, attendants of the Neurology Unit, pediatric department, Menoufia University Hospitals (Group Ι). The patients were sub-classified into two groups, according to response to anti-epileptic treatment; Group Ι a (drug responder) and Group Ι b (drug-resistant). Evenly divided number of apparently healthy, age and gender-matched children were selected as controls (Group II). A complete history, throughout the systemic examination and radiological & metabolic assessment, whenever needed was provided, all participants were genotyped for SCN2A rs17183814 polymorphism by Restriction Fragment Length Polymorphism (PCR-RFLP). Both of A allele and AA, GA genotypes of SCN2A c. 56 G/A were detected more in patients with febrile seizure plus comparison to the control group with a statistically significant difference at frequencies of 17% and 11% and 12% respectively; OR (CI95%): 10.04 (3.49-28.87) and p <0.001. On classifying epileptic patients into 2 subgroups, carriers of SCN2A rs17183814 AA genotype tended to respond poorly to Anti-epileptic Drugs (AEDs). Moreover, multivariate analysis revealed that rs17183814 A allele and positive family history of epilepsy were considered the highest predicted risk factors for the development of epilepsy; p<0.05. SCN2A rs17183814 (A) allele was specifically associated with developing febrile seizure plus and could modulate the patient's response to anti-epileptic medications.

Protocadherin 19 (PCDH19) gene is one of the most common genes involved in epilepsy syndromes. According to literature data PCDH19 is among the 6 genes most involved in genetic epilepsies. PCDH19 is located on chromosome Xq22.1 and is involved in neuronal connections and signal transduction. The most frequent clinical expression of PCDH19 mutation is epilepsy and mental retardation limited to female (EFMR) characterized by epileptic and non-epileptic symptoms affecting mainly females. However, the phenotypic spectrum of these mutations is considerably variable from genetic epilepsy with febrile seizure plus to epileptic encephalopathies. The peculiar exclusive involvement of females seems to be caused by a cellular interference in heterozygosity, however, affected mosaic-males have been reported. Seizure types range from focal seizure to generalized tonic-clonic, tonic, atonic, absences, and myoclonic jerks. Treatment of PCDH19-related epilepsy is limited by drug resistance and by the absence of specific treatment indications. However, seizures become less severe with adolescence and some patients may even become seizure-free. Non-epileptic symptoms represent the main disabilities of adult patients with PCDH19 mutation. This review aims to analyze the highly variable phenotypic expression of PCDH19 gene mutation associated with epilepsy.