Hoyeraal-Hreidarsson syndrome (HHS) is a severe infantile variant of X-linked dyskeratosis congenita (DC). The authors report evidence of increased in vitro sensitivity to radiation and alkylating agent in circulating lymphocytes and fibroblasts obtained from a 7-year-old boy with HHS. A major telomere shortening was also found (3 kb) as compared to healthy donors (10 kb). The standard treatments, chemotherapy regimens, and radiation therapy were not possible. The data suggest that conditioning regimens including TBI should not be used when a bone marrow transplantation procedure is planned in these patients.