ObjectiveTo study SCN1A gene mutations and their inheritance in patients with Dravet syndrome (DS), and to analyze the phenotypes of their family members. MethodsGenomic DNA was extracted from peripheral blood samples from DS patients and their parents. SCN1A gene mutations were screened using PCR-DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Results547 DS patients were collected, SCN1A gene mutations were identified in 379 patients (69.3%), which included 179 missense mutations (47.2%), 78 nonsense mutations (20.6%), 77 frameshift mutations (20.3%), 37 splice site mutations (9.8%), and 8 cases with SCN1A gene fragment deletions or duplications (2.1%). Of 379 DS patients, the parents of 354 DS patients were further analyzed, the de novo mutations accounted for 92.9%, inherited mutations accounted for 7.1%, and in 5 of the latter families, the SCN1A-positive parent carried a somatic mutations mosaicism. For the 25 parents carrying SCN1A mutations, 1 had DS, 11 had febrile seizures plus, 9 had febrile seizures, whilst 4 were normal. ConclusionsThe mutation rate of SCN1A in DS patients is high. Most mutations are of missense and truncation mutations (including nonsense mutation and frameshift mutation). Only a few patients have carried fragment deletions or duplications. Most SCN1A mutations are de novo, only a few are inherited from the parents. SCN1A mutations carried by the parents can be in the form of mosaicism. The phenotypes of parents with SCN1A mutations can be severe, mild or normal, and a mosaic transmitting parent always shows mild or normal.
ObjectiveTo explore the effect of Ketogenic diet (KD) in patients with Dravet syndrome (DS).MethodsThe seizures, electroencephalogram (EEG) and cognitive function of 26 DS patients receiving treatment of KD from June 2015 to October 2019 in the Epilepsy Centre of Guangdong 999 Brain Hospital were analyzed retrospectively. Modified Johns Hopkins protocol was used to initiate KD, blood glucose and urinary ketone bodies were monitored in the patients. The effect was evaluated by Engel outcome scale. And the EEG, cognition, language and motor function of the patients were assessed.Results26 DS patients (20 boys, 6 girls) received treatment of KD more than 4 weeks, the seizure of epilepsy were reduced above 50% in 15 patients (57.7%), 2 patients were seizure free. Among them, the effcet of KD can be observed in 7 patients within one week and 3 patients within two weeks, accounting for 66.7% (10/15). 26 cases (100%), 24 cases (92.3%), 20 cases (76.9%), 11 cases (42.3%) were reserved in 4, 12, 24, 28 weeks respectively. 26 patients achieved Engel Ⅰ ,Ⅱ,Ⅲ,Ⅳgrade effect, accounting for 38.5% (10/25), 54.2% (13/23), 65.0% (12/19), 81.8% (9/11) respectively according to Engel scale. The back ground rhythm of EEG showed obvious improvement in 14 patients wthin 16 patients who revieved EEG after KD. 17 patients assessed cognitive, language and motor function after KD, cognitive function was improved in 10 patients, language was enhanced in 11 patients, motor function of 8 patients was enhanced. The main adverse reactions of KD in the treatment process were mainly gastrointestinal symptoms and metabolic disorders.ConclusionKD treatment in DS has many advantages, such as fast acting, being effective in more than half of the DS patients and tolerable adverse reactions. Cognitive, language and motor function were improved in some patients. Drug resistant DS patients are suggested to receive KD treatment early.
ObjiectiveTo explore the efficacy and safety of ketogenic diet therapy (KDT) in the rapidly progressive stage of childhood developmental epileptic encephalopathy Dravet syndrome (DS). Methods The clinical data of all patients who added KDT in the Children’s Hospital of Fudan University from 2011 to 2022 were retrospectively collected, and the age of <6 years was used as the criterion for the rapid progression of the disease. The clinica data, genotype and the efficacy of KDT were analyzed in DS patients who met the criteria. Results A total of 32 patients met the criteria for rapid disease progress, including 22 males and 10 females. The age at onset was (5.69±2.10) months. All patients had multiple seizure phenotypes and monthly seizures despite reasonable Antiseizure medications treatment. After 3, 6, 12, and ≥24 months, 93.8% (30/32), 87.5% (28/32), 53.1% (17/32), 34.4% (11/32) remained on the KDT, while 76.7% (23/30), 75.0% (21/28), 70.6% (12/17), 54.5% (6/11) showed >50% reduction in seizure. Status epileptius (SE) was reduced by 100% at 3 months, 71.0% at 6 months, 86.0% at 12 months. After 12 months, 14 patients experienced efficacy degradation. After 3 months, the EEG background rhythm showed improvement in 75.0% patients, interictal epileptic discharges was decreased in 54.5% patients and cognitive function was improved in 78.6% patients. At the initial stage of KDT, 62.5% (20/32) patients had transisent adverse reactions, including diarrhea, vomiting, fatigue, lethargy, hypoglycemia, and metabolic acidosis, but no mid- and long-term adverse reactions were found. ConclusionKDT is an efficective and safe treatment for DS. KDT can effectively control seizures, reduce the incidence of Status SE and shorten the duration of SE. With the prolongation of the KDT course, some patients experienced a degraded effect. KDT can improve abnormal EEG and cognitive function in DS patients. Pharmoco-resistant DS patients are suggested to receive KDT in the early stage of disease progression.