We studied the responses of several dyskeratosis congenita (DC) cell lines to the DNA strand-cleaving and base-damaging agent bleomycin. Fibroblasts, peripheral blood lymphocytes, and transformed lymphoblasts of six DC patients and an obligate DC heterozygote showed more chromatid breaks than did respective controls exposed to various concentrations of bleomycin during the G₂ phase of the cell cycle (P < 0.0001). Unsynchronized DC fibroblasts in culture also showed decreased survival, compared to normals, following bleomycin treatment. DC lymphocytes teated with bleomycin for the final 24 h of culture showed more chromatid- and chromosome-type damage than did normals (P < 0.0001) or G₀-treated DC lymphocytes. Spontaneous chromosome breakage was normal in all six DC cell lines. The ability to distinguish affected and heterozygous DC cells without spontaneous chromosome instability from normals on the basis of their bleomycin hypersensitivity provides a marker for future studies of the pathogenesis of this disorder.

Objective: The 4q– syndrome comprises all microscopically visible deletions of the long arm of chromosome 4. Cases with 4q deletions represent a diverse group that share several phenotypic characteristics. We report the prenatal diagnosis of an isolated terminal 4q33 deletion in a fetus with hydrops. Method: A comprehensive workup, including an amniocentesis, was performed on a 32-week fetus presenting with massive hydrops and polyhydramnios. Results: The karyotype obtained from the amniotic fluid showed an unusual banding pattern on chromosome 4q. Fluorescent in situ hybridization revealed a 4q33-qter deletion. The proband shared several of the phenotypic characteristics of the 4q– syndrome. Multidisciplinary evaluation of the newborn confirmed the genotype and failed to identify another cause for the hydrops. Conclusion: We suggest that the broad spectrum of phenotypes expressed by patients with terminal 4q33 deletions includes hydrops fetalis.

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