Chipping away at the common epilepsies with complex genetics: the 15q13.3 microdeletion shows the way.
The idiopathic epilepsies are genetically heterogeneous with more than 50 clinical classifications. They are characterized by episodic seizures arising from erratic neuronal discharge in susceptible individuals. The most common predisposing genetic cause is the recently discovered chromosome 15q13.3 microdeletion. Other disorders previously attributed to the same lesion include autism, intellectual disability and schizophrenia. This phenotypic spectrum is most easily imagined as a contiguous gene syndrome with idiopathic generalized epilepsy as the most common clinical manifestation. Expressivity of the microdeletion in carriers is too variable for antenatal prediction of phenotype to be possible; however, when it is detected in living affected cases, it can be taken as the major predisposing cause for the observed phenotype. The discovery of this small 15q13.3 lesion barely scratches the surface that conceals what we ultimately need to know about the molecular genetic mechanisms behind the common epilepsies with complex genetics, but it provides valuable insight into how to proceed toward that goal.
Mulley
John C
JC
Epilepsy Research Program, Genetics and Molecular Pathology, SA Pathology at the Women's and Children's Hospital, 72 King William Road, North Adelaide, SA 5006, Australia.
Dibbens
Leanne M
LM