Autosomal recessive rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp: Delineation of the syndrome and gene mapping to chromosome 16p12-11.2

We describe a pedigree in which 3 members in the same generation are affected by Rolandic epilepsy (RE), paroxysmal exercise-induced dystonia (PED), and writer's cramp (WC), Both the seizures and paroxysmal dystonia had a strong age-related expression that peaked during childhood, whereas the WC, also appearing in childhood has been stable since diagnosis. Genome-wide linkage analysis performed under the assumption of recessive inheritance identified a common homozygous haplotype in a critical region spanning 6 cM between markers D16S3133 and D16S3131 on chromosome 1.6,. cosegregating with the affected phenotype and producing a multipoint LOD score value of 3.68. Although its features are unique, this syndrome presents striking analogies with the autosomal dominant infantile convulsions and paroxysmal coreoathetosis (ICCA) syndrome, linked to a 10 cM region between D16S401 and D16S517, which entirely includes the 6 cM of the RE-PED-WC critical region. The same gene map be responsible for both RE-PED-WC and ICCA, with specific mutations explaining each of these Mendelian disorders. This report shows that idiopathic focal disorders such as epilepsy and dystonia, can. be caused by: the same genetic abnormality, may have a transient expression, and may be inherited as an autosomal recessive trait.