Two studies have previously suggested that HHS might arise as a result of defects in telomere biology other than just length. Touzot et al.23 showed that individuals with HHS can have a variety of telomere defects. Critically short telomeres are not inevitably associated with this severe phenotype, and additional factors, some of which are involved in telomere protection and/or replication, might cause some cases of HHS. Lamm et al.12 presented findings on a family reported here (DCR family 103) and noted that leukocyte telomeres were severely short (as observed in our study) but that fibroblast telomeres were of normal length. They also found that the 3′ single-stranded overhang was reduced in both cell types and that the catalytic telomerase core functioned normally. Mutations identified in RTEL1 might now explain some of their observations.