Abstracts

Rationale: Children with rolandic epilepsy (RE) are at sixfold increased risk for reading disability (RD) and approximately two-thirds of RE patients are affected by RD. Relatives of RE patients are at three times higher risk for RD, but the risk is dependent on the RD status of the proband (Clarke et al, 2007). These observations suggested a genetic basis for RD in RE families, rather than a model in which RD is a consequence of recurrent seizures. We therefore tested for linkage of RD in a genomewide linkage analysis.Methods: We performed a genomewide screen for RD in 22 families each ascertained through a single individual with stringently defined RE. RD was defined by ICD-10 criteria, excluding sensory and social risk factors for dyslexia. STR markers were typed at an average density of 4cM. We used two point and multipoint linkage analysis with the MMLS approach.Results: In two point analyses we found lod scores exceeding 2.0 on chromosomes 1, 2, 6 and 7. The maximum two-point lod score was 3.21, dominant with 55% penetrance, on chromosome 7. We obtained an HLOD of 2.83 at the same marker under multipoint analysis, also under a dominant 50% penetrant model.Conclusions: Reading disability in RE is a complex genetic disorder, with contributions from several genetic loci. These loci are genetically heterogeneous to those reported in non-syndromic dyslexia. Loci for RD may contribute to the complex genetic model of RE.