N Syndrome

Hess et al. (1974) described what at first appeared to be a relatively nondescript mental retardation syndrome in 2 brothers. Features included visual impairment, deafness, laterally overlapping upper eyelids, large corneas, abnormal auricles, cryptorchidism, hypospadias and spasticity. It was designated by the initial of the surname. At the time of the report, 1 of the brothers had died at the age of 5.5 years of lymphoblastic leukemia with a mediastinal mass. The features of the syndrome and its possible genetics were expanded by the follow-up given by Hess et al. (1987). The mother of the propositi, a woman who had none of the manifestations of the syndrome, died at age 37, reportedly of leukemia. The second propositus also died of lymphoblastic leukemia with a mediastinal mass and leukemic infiltration of tissues in a pattern similar to that seen in his brother. Hess et al. (1987) demonstrated increased chromosome breakage in the affected brothers and in their unaffected mother. Hess et al. (1987) suggested that the N syndrome is X-linked recessive. Floy et al. (1990) found that bleomycin, which is known to break double-stranded DNA, produced increased chromosome breakage in normal control, Fanconi anemia, and N syndrome fibroblasts. When aphidicolin was used to inhibit repair mediated by DNA polymerase alpha (312040), both normal control and Fanconi anemia fibroblasts showed significantly more chromosome breakage than was produced by bleomycin alone, but there was no increase in the amount of breakage seen in the N syndrome fibroblasts over that seen with bleomycin alone. The results suggested to Floy et al. (1990) that a mutation in DNA polymerase alpha is responsible for this syndrome.