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 their relative advanced age at the time when SCI was ascertained. We have also shown that NBS patients can be diagnosed earlier and the disease sufficiently confirmed on the basis of congenital microcephaly and on the direct detection of 657de15 mutation in NBS1 gene. Genealogical analysis of families with SCI revealed a low risk of prenatal selection of affected homozygotes and high cancer prevalence in relative (in NBS families recognized heterozygotes) at young adult age. Due to severe DNA repair disorder and hyperradiosensitivity of affected homozygotes as well as unaffected heterozygotes, conventional diagnostics and treatment protocols of lymphoreticular malignancies in affected homozygotes are prohibited. The use of Nijmegen treatment protocol improved in our patients dramatically their clinical prognosis, which is documented by 6 NBS patients surviving one or two malignancies. Early diagnose of SCI and information for families and their doctors about consequences of DNA repair disorder and about their hyperradiosensitivity is essential for improving the clinical prognosis of SCI patients.

Oddĕlení klinické genetiky Ustavu biologie a lékarské genetiky 2 LF UK Praha

Diagnosis of Bloom Syndrome in a Patient with Short Stature, Recurrence of Malignant Lymphoma, and Consanguineous Origin