Clinical spectrum and genetics of dyskeratosis congenita (DC). Since the identification of the DC genes and the application of genetic testing, it is increasingly recognized that the classic DC clinical features represent the “tip of the iceberg” and are present in only a small proportion of patients. Instead, a substantial proportion of patients present without mucocutaneous manifestations, but with aplastic anemia (AA) or myelodysplastic syndrome (MDS). In other patients, extrahematopoietic manifestations may be the primary or only manifestations of disease, such as pulmonary fibrosis (PF), liver fibrosis (LF) or osteoporosis (OP). In rare cases, certain types of cancer occur at unexpectedly young ages or acute myeloid leukemia (AML) is the presenting feature. In addition to clinically affected individuals, a significant population of silent mutation carriers exists with no obvious disease manifestations. Clinic represents the clinical spectrum from silent mutation carriers to individuals with severe disease manifestations. The triangle on the right illustrates the age when telomeres become critically short; in severe disease, telomeres are short at a young age, whereas in individuals with mild disease, telomeres become critically short later in life. M indicates mutant; and WT, wild type. Professional illustration by Marie Dauenheimer.