Swedish Population Study Highlights Advances in Dravet Diagnosis, Care

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The prevalence of Dravet syndrome in Sweden was one in 45,000 at the end of 2018, with most identified patients having a disease-causing mutation in the SCN1A gene, a study found.

Data showed the rate of new diagnoses was higher, the age at diagnosis lower, and the use of contraindicated sodium channel blocking medication less frequent in more recent years, likely reflecting “improved diagnostic and therapeutic procedures and increased awareness of the disease,” the researchers said.

The study, “Dravet syndrome in children—A population-based study,” was published in Epilepsy Research. 

Dravet syndrome is a rare, severe form of treatment-resistant epilepsy usually caused by mutations in the SCN1A gene. Children with Dravet have multiple seizure types that usually emerge during the first year of life, in addition to symptoms that include intellectual disability, autism spectrum disorder, and movement problems.

The incidence of Dravet is believed to be somewhere between one in 16,000 to 46,000 live births, but variations in diagnostic criteria have made its true prevalence difficult to determine.

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Researchers conducted a population-based study to identify and characterize children living with Dravet in Sweden. They identified 55 children with Dravet between 2000 and 2018, 48 of whom were alive as of December 31, 2018.

Based on these 48 children, the prevalence of Dravet in Sweden was determined to be one in 45,000 people at the end of 2018.

Results showed the median age at diagnosis was 2 years. The researchers also found that in younger children born between 2010–2018, the age at diagnosis and genetic testing were significantly lower than in children born before 2010.

The cumulative incidence of Dravet, reflecting the rate of new cases, was also higher between 2010 and 2018 at one in 33,000 than before 2010 at an incidence rate of one in 46,000.

“The increased [cumulative incidence] and reduced age at diagnosis in the younger age group is in line with the view that the awareness of rare diseases like [Dravet] tend to improve with time,” the researchers wrote.

Of the seven children that died, the median age at death was 4.7 years. Reasons for death included definite, probable or possible sudden unexpected death in epilepsy (SUDEP), brain injury resulting from seizure-induced respiratory distress, pneumonia, and pneumonitis. All the children who died carried a disease-causing mutation in SCN1A. 

In 49 out of 53 children for whom genetic testing data were available, a disease-causing SCN1A mutation was found, and SCN1A mutations of unknown significance were found in another two children. For all but four children, these mutations were de novo, meaning they were not inherited from either parent. For the two children without SCN1A mutations, no disease-causing mutation was found.

For the remaining analyses of clinical disease characteristics, 42 children were included. Among them, the median age at the first seizure was 5 months and the age at epilepsy diagnosis was 1o months. All the children had ongoing seizures of various types.

All had a history of febrile, or fever-induced seizures, and most (90%) had a history of convulsive status epilepticus, a prolonged seizure lasting at least five minutes.

A type of seizure called tonic seizure, marked by sudden muscle stiffening, occurred in 60% of children. This seizure type was previously considered unusual in Dravet and will need to be confirmed in larger studies, the research team noted.

The children were treated with a median of three anti-seizure medications. The most commonly used medications included valproate (100%), benzodiazepines (95%), levetiracetam (83%), and sodium channel blockers (62%). Older children born before 2010 were more likely to have used sodium channel blockers or topiramate than younger children, and sodium channel blockers were currently used in only four children.

Sodium channel blockers are now usually contraindicated in children with Dravet, which likely explains their recent lower use, the researchers suggested.

Intellectual disability was observed in 28 children (67%) and autism spectrum disorder in 19 (45%). Nine children had neither diagnoses.

The findings provide a snapshot of the incidence and clinical characteristics of Dravet syndrome in Sweden.

There are currently no universal screening programs for Dravet in Sweden, and it’s possible that some of those with a diagnosis were not identified in this study, the researchers noted.