BACKGROUND: Dyskeratosis congenita is a cancer-prone bone marrow failure 
syndrome caused by aberrations in telomere biology.
DESIGN AND METHODS: We studied 65 patients with dyskeratosis congenita and 127 
unaffected relatives. Telomere length was measured by automated multicolor flow 
fluorescence in situ hybridization in peripheral blood leukocyte subsets. We 
age-adjusted telomere length using Z-scores (standard deviations from the mean 
for age).
RESULTS: We confirmed that telomere lengths below the first percentile for age 
are very sensitive and specific for the diagnosis of dyskeratosis congenita. We 
provide evidence that lymphocytes alone and not granulocytes may suffice for 
clinical screening, while lymphocyte subsets may be required for challenging 
cases, including identification of silent carriers. We show for the first time 
using flow fluorescence in situ hybridization that the shortest telomeres are 
associated with severe variants (Hoyeraal-Hreidarsson and Revesz syndromes), 
mutations in DKC1, TINF2, or unknown genes, and moderate or severe aplastic 
anemia. In the first longitudinal follow up of dyskeratosis congenita patients, 
we demonstrate that telomere lengths decline with age, in contrast to the 
apparent stable telomere length observed in cross-sectional data.
CONCLUSIONS: Telomere length by flow fluorescence in situ hybridization is an 
important diagnostic test for dyskeratosis congenita; age-adjusted values 
provide a quantitative measure of disease severity (clinical subset, mutated 
gene, and degree of bone marrow failure). Patients with dyskeratosis congenita 
have accelerated telomere shortening. This study is registered at 
www.clinicaltrials.gov (identifier: NCT00027274).