Dyskeratosis congenita is a chromosomal instability disorder.

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by dystrophic changes in the skin and mucous membranes, bone marrow failure, and a predisposition to malignancy. In the majority of families the pattern of inheritance of DC has been compatible with X-linkage, the most likely location being Xq28. The primary defect responsible for this disease remains unknown. As DC shares many features (congenital abnormalities, bone marrow failure) with the chromosomal instability disorder. Fanconi's anaemia (FA), several studies have focused on cytogenetic features in DC. Unlike in FA, cytogenetic studies on peripheral blood lymphocytes have shown no significant difference between DC and normal lymphocytes with or without prior incubation with clastogens (bleomycin, diepoxybutane, mitomycin-c, 4-nitroquinoline-1-oxide). However, studies on DC fibroblasts have shown abnormalities in both morphology (polygonal cell shape, ballooning, dendritic-like projections) and growth rate (doubling time about twice normal), as well as numerous unbalanced chromosomal rearrangements (dicentrics, tricentrics, translocations) in the absence of any clastogenic agents. Bone marrow metaphases from one out of three patients studied (the eldest of the three) also showed unbalanced chromosomal rearrangements in the absence of any clastogens. Cell-specific difference and a higher rate of chromosomal rearrangements in the older patients appear to correlate with the clinical evolution of the disease. These findings suggest that the DC defect predisposes DC cells to developing chromosomal rearrangements.