This scientific commentary refers to ‘Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?’, by Wandschneider et al. (doi: 10.1093/brain/awu175).
In this issue of Brain, Wandschneider and colleagues (2014) report that relatives of patients with juvenile myoclonic epilepsy (JME) show changes in functional MRI, indicating altered motor system activation and functional connectivity, similar to those seen in patients themselves (Vollmar et al., 2011). This study reflects the maturation of the field of imaging, particularly the use of advanced functional MRI analysis. Why is this of interest? We see two major potential contributions of these data; first, the concept of an imaging endophenotype and its specificity and, second, further understanding of the fundamental disease mechanism.
Complex disorders and imaging endophenotypes
Juvenile myoclonic epilepsy is an important epilepsy syndrome because it is common and easily treatable, yet often misdiagnosed. It belongs to the family of generalized epilepsies, formally designated as ‘idiopathic’ or ‘primary’, but now referred to as genetic generalized epilepsies because of the strong evidence of genetic aetiology (Berg et al., 2010), although the specific genetic determinants remain largely elusive. A few very rare families segregate an autosomal dominant gene, the best documented cases being mutations in the GABRA1 gene, which encodes a GABA receptor subunit. Clinical genetic evidence derived from family studies and twin analyses strongly supports the contention that juvenile myoclonic epilepsy is a complex disorder with multiple genetic components (see Helbig et al., 2008 and references therein). Deep sequencing has …