Chromosomal Instability Syndromes

Overview

We refer 55 cases of the chromosomal instability syndromes (SCI), diagnosed in patients of our genetical clinics.Problems of early diagnosis can be documented by a discrepancy between the expected number of patients and theirrelative advanced age at the time when SCI was ascertained. We have also shown that NBS patients can be diagnosedearlier and the disease sufficiently confirmed on the basis of congenital microcephaly and on the direct detection of657del5 mutation in NBS1 gene. Genealogical analysis of families with SCI revealed a low risk of prenatal selectionof affected homozygotes and high cancer prevalence in relative (in NBS families recognized heterozygotes) at youngadult age. Due to severe DNA repair disorder and hyperradiosensitivity of affected homozygotes as well as unaffectedheterozygotes, conventional diagnostics and treatment protocols of lymphoreticular malignancies in affectedhomozygotes are prohibited. The use of Nijmegen treatment protocol improved in our patients dramatically theirclinical prognosis, which is documented by 6 NBS patients surviving one or two malignancies. Early diagnose ofSCI and information for families and their doctors about consequences of DNA repair disorder and about theirhyperradiosensitivity is essential for improving the clinical prognosis of SCI patients.

Key words:
genetic instability, Nijmegen breakage syndrome, malignancies, radiosensitivity, microcephaly,growth retardation.