Genomewide linkage scan of the photoparoxysmal response (PPR) and exploration of its relationship to Idiopathic Generalised Epilepsies (IGE)

Photosensitivity or photoparoxysmal response (PPR) is an epilepsy-related electroencephalographic trait evoked by standardised intermittent photic stimulation. It is characterised by a brain response with spike wave discharges, ranging from occipital spikes only to generalised spike waves (type I – IV). PPR is a common finding in the general population (up to 8%) and is frequently associated with idiopathic epilepsies. It has an especially high prevalence (up to 90%) in idiopathic generalised epilepsies (IGE). The molecular genetic dissection of the photoparoxysmal response as an endophenotype seems to be a suitable approach to elucidate the molecular genetic basis of IGE.

We present the results of a genomewide linkage scan designed to map susceptibility loci for PPR and to explore its genetic relationship with IGE. We included 60 families of German origin with at least two siblings affected by PPR. To dissect PPR specific loci and their relation to IGE susceptibility loci, we phenotypically defined two distinct family subgroups. The first group comprised 19 families with predominantly pure PPR and photosensitive seizures (PPR-families), whereas 25 families, strongly associated with IGE, were included in the second subgroup (PPR/IGE-families). MOD-score analyses provided significant evidence for linkage to the region 6p21.2 in the PPR-families, and suggestive evidence for linkage to the region 13q31.3 in the PPR/IGE families, both with a best-fitting recessive mode of inheritance. Our study reveals two PPR-related susceptibility loci correlating with the family history of IGE. The locus on 6p21.2 seems to predispose to PPR itself, whereas the locus on 13q31.3 also confers susceptibility to IGE.