Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1

Shortened telomeres can cause a wide variety of clinical features that constitute a phenotypic spectrum. The most severe form is dyskeratosis congenita (see, e.g., 127750), characterized by early childhood onset of skin abnormalities, bone marrow failure, predisposition to malignancy, and risk of pulmonary and hepatic fibrosis. Adult-onset pulmonary fibrosis is the most common manifestation of mutant telomerase genes. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Phenotype, age at onset, and severity are determined by telomere length, not just telomerase mutation (summary by Armanios, 2009). The genetic diagnosis of telomere-related bone marrow failure and pulmonary fibrosis has implications for treatment because affected individuals generally do not respond to immunosuppression and may be at increased risk for fatal complications after bone marrow or lung transplantation (Parry et al., 2011). Genetic Heterogeneity of Telomere-Related Pulmonary Fibrosis and/or Bone Marrow Failure Also see PFBMFT2 (614743), caused by mutation in the TERC gene (602322) on chromosome 3q26; PFBMFT3 (616373), caused by mutation in the RTEL1 gene (608833) on chromosome 20q13; PFBMFT4 (616371), caused by mutation in the PARN gene (604212) on chromosome 16p13; and PFBMFT5 (618674), caused by mutation in the ZCCHC8 gene (616381) on chromosome 12q24.

OMIM