A new chromosomal instability disorder: the Nijmegen breakage syndrome

A 10-year-old boy with microcephaly, stunted growth, mental retardation, café-au-lait spots and immunodeficiency is described. An older brother of the patient had the same clinical symptoms and a more severe immunodeficiency. Cytogenetic studies in the proband revealed a typical form of chromosome instability with multiple rearrangements of chromosomes 7 and 14. Such abnormalities were also present, though in very low frequencies, in the father and three of the phenotypically normal sibs. The similarity of the symptoms in the two sibs, the close consanguinity of their parents and the results of the cytogenetic studies in the family favour the hypothesis that the disorder is an inherited one. The clinical features and the chromosome aberrations as present in the proband are usually found in chromosomal breakage syndromes, but it was possible to exclude each of the classical chromosomal breakage syndromes on clinical and/or cytogenetic grounds.