Alejandra Viviescas, PhD, —

Confirmation of Dravet syndrome by genetic analysis and identification of gene mutations is important to provide patients with adequate treatment and follow-up, according to a case report. The report, "Dravet Syndrome in Lebanon: First Report on Cases with SCN1A Mutations," was published in Case Reports in Medicine. Dravet syndrome is a genetic disorder that causes severe epilepsy and appears in the first year of life. In most cases, the cause is a de novo mutation — one that appears for the first time in an individual, instead of being inherited from the parents. About 80 percent of patients have mutations in the SCN1A gene that holds the instructions to produce a specific subunit of a sodium channel. Sodium channels are essential for the transmission of electric signals between nerve cells. Researchers reported the case of eight unrelated Lebanese children, aged 6 to 18 months, who were referred for genetic counseling from January 1999 to December 2016 due to suspicion of Dravet syndrome. None of the children had a family history of seizures or neurologic disease. All children began to have seizures after the age of 5-6 months. The first seizures were short and triggered by fever, but they later became longer, without fever, and required acute treatment to stop the convulsions. The patients experienced one to four seizures per month. Five children had generalized seizures — affecting both brain hemispheres and accompanied by jerking movements of the four extremities. The remaining three children had focal seizures, affecting only one brain hemisphere. The seizures did not respond or responded only partially to anti-epileptic medications; in three of the patients neurocognitive decline was already present. The researchers performed a genetic analysis of the SCN1A gene to search for possible mutations that could confirm a Dravet diagnosis. Seven children had de novo mutations in different exons of the SCN1A gene (exons are sections of a gene that contain the information to produce proteins). Four mutations had not been described previously. All mutations were heterozygous (present in only one copy of the gene, we have two copies of each gene, one from each parent) and considered pathogenic (disease-causing) or likely pathogenic. In five cases, the mutation caused one amino acid to change, altering the function of the protein. In one case the mutation caused the formation of the protein to stop prematurely. In the remaining case the mutation caused the exons of the protein not to be assembled correctly. After the diagnosis, three patients were lost to follow-up, two died before the age of 7, and the remaining three had persistent seizures despite the administration of anti-epileptic medicines. "In Lebanon, this is the first study series on DS. The patients of the present series had the typical signs and symptoms of [Dravet syndrome]: febrile [feverish] seizures before the age of 1 year, prolonged seizures resistant to treatment, clinical deterioration with time, and no family history of seizure," researchers wrote. Researchers estimate a prevalence of Dravet syndrome of one in 90,000 children in Lebanon. "This low proportion of cases is most probably due to the fact that [Dravet syndrome] cases are not diagnosed, or misdiagnosed with any febrile seizure or neurological problem, or because of lack of follow-up and unavailability of genetic tests," they explained. A correct and early diagnosis is important to guarantee that patients receive the best treatment as early as possible, including medications such as stiripentol, valproate, benzodiazepine or topiramate, control of external factors such as infections and body temperature variations, as well as diet (e.g., ketogenic diet). "It is important to note that many of the patients are under-treated and do not receive the standard care for [Dravet syndrome] due to incorrect diagnosis. The patients reported herein had their symptoms improve while on valproate, topiramate, levetiracetam, and phenobarbital. These drugs help only in reducing the severity of the seizures, without complete eradication of the disease," researchers wrote. The team recommended a close follow-up of Dravet cases "to prevent such hurdles and to have a multidisciplinary specialized follow-up, with pediatricians, nurses, psychologists, physiotherapists, a home care team, and an educational system to patients and their parents."

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Alejandra Viviescas, PhD, —

Articles by Alejandra Viviescas

Case Report of Lebanese Children With Dravet Syndrome Underscores Importance of Genetic Diagnosis

Rare Disease Day 2023

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