Unverricht-Lundborg disease in a five-generation Arab family - Instabilityof dodecamer repeats

Background: Unverricht-Lundborg disease (ULD) is the prototypical form of p rogressive myoclonus epilepsy, and subjects are usually very photosensitive . ULD is caused by mutations in the cystatin B (CSTB) gene; the most common mutation is expansion of a dodecamer repeat near the promoter. The authors studied a five-generation Arab family with ULD lacking photosensitivity. M ethods: An Arab family from the Galilee region of Israel with progressive m yoclonus epilepsy was clinically evaluated. Blood samples were obtained fro m three living affected and 16 unaffected individuals. Expansion of dodecam er repeat in the CSTB gene was examined. Results: The three living affected individuals showed spontaneous and action myoclonus, ataxia, and mild deme ntia. EEG in two individuals showed generalized polyspike-wave without phot osensitivity. The family structure with large sibships and multiple consang uineous loops allowed the authors to examine the gene over four generations of adults. The three living affected individuals were homozygous for repea t expansions and 11 of the 16 unaffected family members were heterozygous. Instability was demonstrated by the presence of expansions of different siz es occurring on the same haplotype background in this inbred family. Fragme nt size variations could be unequivocally detected in two sibships. The exp ansions were in the 49 to 54 dodecamer repeat range. Changes in one generat ion were small, 1 to 4 repeat units, consisting of either enlargements or c ontractions. Conclusions: Instability of the expanded dodecamer repeats in the cystatin B gene is frequent. Almost invariably, a small change is obser ved in parent-child transmission. The lack of photosensitivity in this fami ly is unexplained.