Radiation Sensitivity/chromosome Instability Syndrome, Autosomal Dominant

Ishikawa et al. (2000) reported a Japanese family with an autosomal dominant neurodegenerative disorder with mild chromosome instability and radiation sensitivity. Clinical manifestations included short stature, mental retardation, depression, dysarthria, hyperreflexia, and ataxic gait. MRI demonstrated calcification of bilateral basal ganglia, markedly atrophic spinal cord, and degeneration of the white matter. Cytogenetic studies demonstrated several spontaneous chromosome rearrangements at 14q11.2. Pretreatment with radiation or bleomycin resulted in a high rate of chromatid breaks. The patients showed no evidence of immunodeficiency. Ishikawa et al. (2000) suggested that this family may represent a new autosomal dominant degenerative disorder, possibly due to a mutation in a gene responsible for DNA double-strand breakage repair.