Non-myeloablative umbilical cord blood transplantation for atypical dyskeratosis congenita.

BACKGROUND Short telomere syndrome (STS) in children may result in phenotypically heterogenous clinical spectrum ranging from completely asymptomatic to typical dyskeratosis congenita (DC). Patients with this cancer predisposition syndrome may have multiple organ dysfunctions including pulmonary fibrosis, liver cirrhosis, and bone marrow failure. Not all mutations in telomerase or telomere genes have been identified, and STS may pose a diagnostic and management challenge. METHODS A retrospective chart review and literature search were done for this report. RESULTS Here, we report a case of atypical DC with a heterozygous germline missense mutation in the postmeiotic segregation increased 2 (PMS2) gene, exon 5, (c.466A>G (p. Thr156Ala)). The PMS2 (a mismatch repair protein) gene is known to be an important mediator of telomere-induced aging. The patient was transfusion dependent and underwent successful umbilical cord blood transplant using a non-myeloablative regimen with alemtuzumab, fludarabine, cyclophosphamide, and total body irradiation. CONCLUSION In this case of atypical DC with a previously unreported germline missense mutation in PMS2, the patient was successfully treated with an umbilical cord blood transplant with a non-myeloablative regimen.