Scientists say a person who lived 800 years ago is the source of the modern seizure disorder

Scientists in Australia believe they have discovered the centuries-old origin of a rare form of childhood epilepsy caused by a genetic mutation: a common ancestor who lived in Britain about 800 years ago. The finding is particularly significant because hereditary conditions of this type usually do not survive that long long in the population.

Epilepsy is a broad term for recurrent bouts of abnormal brain activity that cause neurological symptoms, the most pronounced of which are seizures. It can have many different causes, including variations in our genes that are passed down between families. When these seizures are accompanied by fever, they are also known as febrile seizures.

This new study, led by researchers from the University of Melbourne Epilepsy Research Centre, studied cases of childhood febrile seizures strongly associated with the SCN1Bc.363C>G variant. This variant has been found among multiple unrelated families in Australia, Great Britain and many of the USA families had a long history of early epilepsy and disorders appears to be a dominant genetic condition, which means a disease that can be caused by only one copy of a bad gene. But the researchers were curious whether this mutation was passed down from a single common ancestor to these affected families, or whether it appeared independently multiple times in human history.

The group attempted to trace the origin of the SCN1Bc.363C>G variant in 14 families with these seizures. They also analyzed genome data from the UK Biobank, a large and long-term study of human health that it also collects their genetic information.

Within the biobank, the researchers identified another 74 individuals with the same variant. And all of these people had similar patterns of other genetic variation surrounding the variant—a group of genes known as a haplotype. It is highly unlikely that all of these people would have the same common haplotype without common ancestry, the researchers say, meaning that the existence of this genetic disease today is likely due to a single ancestor, also known as a founder event. And as far as they can tell, this ancestor lived about 800 years ago.

“Here we provide evidence of a single founder event leading to the SCN1Bc.363C>GQ11 variant in 14 independent families with epilepsy,” the authors wrote in their paper, Published Tuesday in The American Journal of Human Genetics.

There are other genetic disorders or traits that can clearly be traced back to a single founder event. But these disorders usually appear later in life (after the person has already reproduced) or be recessive, meaning they only cause the disease if someone inherits both copies of the bad variant. So it is very unusual to see the same with a deleterious dominant mutation that appears in childhood. Often, these mutations are removed in a short time, since affected people are less likely to survive into adulthood and pass the mutation on to the next generation — an example of natural selection.

The authors speculate that this mutation may have persisted because most people with it experience relatively mild seizures. ONOnly about 70% of people with the mutation appear to develop the disease at all, which is known as incomplete penetrance. In other words, this mutation could cause problems, but not enough to prevent people who had it from living their lives and passing on their genes.

In addition to learning more about the disease, the authors say their findings could have broader implications. It is possible that there are other genetic mutations that similarly persist in the population at low levels, but which may actually prove to be more harmful than currently assumed.

“These findings suggest that variants present in the population at low frequencies should be considered potentially pathogenic in mild phenotypes with incomplete penetrance and may be more important than previously thought,” they wrote.