Researchers have identified two simple diagnostic criteria to help healthcare practitioners make an early and correct diagnosis of Dravet syndrome in children living in a resource-limited setting in Africa.
The study, “Dravet syndrome in South African infants: Tools for an early diagnosis,” was published in Seizure: European Journal of Epilepsy.
Dravet syndrome is a rare and severe type of epilepsy characterized by prolonged seizures in the first year of a child’s life, which can cause mental and physical problems.
About 70 to 80 percent of cases are caused by mutations in the SCN1A gene, which change nerve cells’ sensitivity to temperature, making warm weather, fevers, or sunlight potential triggers of seizures. Dravet patients often have therapy-resistant and life-threatening seizures, which contribute to a significantly increased premature mortality.
Current treatment is focused on preventing seizures and subsequent cognitive and motor damage. However, the success of this approach is dependent on an early diagnosis and appropriate therapy.
While Africa has the highest burden of epilepsy in the world, mutation-associated epilepsy is underdiagnosed and poorly investigated in the continent. In accordance, the frequency of Dravet syndrome and of its disease-causing mutations within the African population is unknown.
This is mainly due to a general lack of awareness of the disease, a high frequency of seizures being associated with malaria, brain infections, or problems during pregnancy, and lack of access to genetic testing.
Researchers have now evaluated, for the first time, the genetic causes and clinical features of Dravet syndrome in South African children, helping them identify simple diagnostic tools to provide early and cost-effective diagnosis.
The team recruited 22 children (12 girls and 10 boys) with a preliminary diagnosis of Dravet syndrome at the Red Cross Children’s War Memorial Hospital (RCCWMH), in Cape Town.
A genetic analysis on potential Dravet syndrome-causing mutations revealed that nine of the 22 children had mutations in the SCN1A gene and one child had mutations in the PCDH19 gene. Mutations in this last gene are responsible for a rare epilepsy syndrome whose symptoms can overlap or look similar to those in Dravet.
Regarding clinical interventions, “the SCN1A-postitive group was more likely to receive a combination of AEDs [anti-epileptic drugs] (eight out of nine SCN1A-positive patients), whilst 11 out of 12 variant-negative children were managed effectively with monotherapy,” researchers wrote.
The diagnosis of 10 of the 12 children who did not carry any of the studied disease-causing mutations was reevaluated and changed with long-term follow-up: seven were re-diagnosed with febrile seizures plus (FS+), and one with early onset epileptic encephalopathy (EOEE). Perinatal insult and moyamoya disease — a progressive disorder that affects the blood vessels in the brain — were determined as the cause of seizures in the remaining two cases.
This revised diagnosis increased the porpotion of “SCN1A-positive DS [Dravet syndrome] 75%, more in line with international findings,” researchers wrote.
Next, the team conducted statistical analyses to find the clinical features that were most strongly associated with the most common form of the disease, SCN1A-associated Dravet syndrome.
The results showed that seizures before six months of age and a clinical risk score higher than six were significantly associated with SCN1A-related Dravet syndrome. This suggested that these two parameters could be used as “low-cost criteria to identify patients most at risk of DS [Dravet syndrome] and who are likely to benefit from genetic testing,” researchers explained.
The clinical risk score is a screening test developed to predict Dravet syndrome before the child’s first year of life. It consists of a total cumulative score of several predictive risk scores, regarding the age at seizure onset, number of seizures and prolonged seizures, and type and trigger of seizure.
The team noted that while the risk score may require some medical experience to recognize some of its diagnostic markers, the age of seizure onset is simpler and easy-to-implement.
“In the poorly resourced African setting, observing these clinical signs of DS [Dravet syndrome] may go a long way towards embarking on the correct diagnostic course for DS and a better overall outcome,” they added.
Researchers also highlighted the need to raise awareness among healthcare practitioners in Africa of a possible genetic cause behind seizures, “thus beginning to bridge the significant epilepsy treatment gap in Africa,” they concluded.