The OMIM epileptic encephalopathy genes – a 2014 review

EIEE1-19. Online Mendelian Inheritance in Man (OMIM) is one of the most frequently accessed online databases for information on genetic disorders. Genes for epileptic encephalopathies are organized within a phenotypic series entitled Early Infantile Epileptic Encephalopathy (EIEE). The EIEE phenotypic series currently lists 19 genes (EIEE1-19). Let’s review the evidence for these genes as of 2014. Continue reading

TBC1D24, DOORS Syndrome, and the unexpected heterogeneity of recessive epilepsies

The return of TBC1D24. In 2010, the TBC1D24 gene was the first gene for human epilepsies to be discovered through next generation sequencing techniques. Ever since, this gene has been a mystery, as the phenotypes of the families with recessive mutations in this gene varied widely. Now, a recent paper in Lancet Neurology finds recessive TBC1D24 mutations in a large proportion of patients with DOORS syndrome, a rare distinct autosomal recessive syndrome with deafness, onychodystrophy, osteodystrophy, intellectual disability (mental retardation), and seizures. This finding demonstrates that we have only just scratched the surface of the complicated genetic architecture of human epilepsies. Continue reading

The return of TBC1D24

First of its kind. In 2010, a virtually unknown gene became the first epilepsy gene to be discovered through massive parallel sequencing techniques. This gene, TBC1D24, was found in two recessive families with different types of epilepsy. Afterwards, it became silent around this gene with no further findings. Now, a recent paper reports on a third family with a mutation in this gene with a complex phenotype of epileptic encephalopathy and movement disorders. As the mutation is located in an alternative exon of this gene, this raises important issues on how we identify and interpret mutations. Continue reading