A NEW CHROMOSOMAL INSTABILITY DISORDER: THE NIJMEGEN BREAKAGE SYNDROME

TLDR

The study reports a 10‑year‑old boy with microcephaly, growth retardation, intellectual disability, café‑au‑lait spots, and immunodeficiency, whose older brother shows similar but more severe symptoms, and whose clinical and cytogenetic profile resembles chromosomal breakage syndromes yet excludes the classical forms. Cytogenetic analysis revealed chromosome 7 and 14 rearrangements in the proband, with low‑frequency similar abnormalities in the father and three unaffected siblings, supporting an inherited chromosomal instability disorder. Authors: Weemaes, Hustinx, Scheres, van Minister, Bakkeren, and Taalman from the University of Nijmegen, Paediatrics and Human Genetics.

Abstract

ABSTRACT. Weemaes, C. M. R., Hustinx, T. W. J., Scheres, J. M. J. C, van Minister, P. J. J., Bakkeren, J. A. J. M. and Taalman, R. D. F. M. (Departments of Paediatrics and Human Genetics, University of Nijmegen, Nijmegen, The Netherlands.) Acta Paediatr Scand, 70:557,.–A 10-year-old boy with microcephaly, stunted growth, mental retardation, cafe-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.