Description from OMIM

Dyskeratosis congenita is a rare multisystem disorder caused by defective telomere maintenance. Clinical features are highly variable and include bone marrow failure, predisposition to malignancy, and pulmonary and hepatic fibrosis. The classic clinical triad of abnormal skin pigmentation, leukoplakia, and nail dystrophy is not always observed. Other features include premature graying of the hair, osteoporosis, epiphora, dental abnormalities and testicular atrophy, among others (review by Bessler et al., 2007 and Bessler et al., 2010). Hoyeraal-Hreidarsson syndrome (HHS) refers to a clinically severe variant of DKC that is characterized by multisystem involvement and early onset in utero. Patients with HHS show intrauterine growth retardation, microcephaly, delayed development, bone marrow failure resulting in immunodeficiency, cerebellar hypoplasia, and sometimes enteropathy. Death often occurs in childhood (summary by Walne et al., 2013). Genetic Heterogeneity of Dyskeratosis Congenita and Hoyeraal-Hreidarsson Syndrome Dyskeratosis congenita is a genetically heterogeneous disorder, showing autosomal recessive, autosomal dominant, and X-linked inheritance. Additional autosomal dominant forms include DKCA2 (613989), caused by mutation in the TERT gene (187270) on chromosome 5p15; DKCA3 (613990), caused by mutation in the TINF2 gene (604319) on chromosome 14q12; DKCA4 (see 615190), caused by mutation in the RTEL1 gene (608833) on chromosome 20q13, DKCA5 (268130), caused by mutation in the TINF2 gene (604319) on chromosome 14q12, and DKCA6 (616553), caused by mutation in the ACD gene (609377) on chromosome 16q22. Autosomal recessive forms include DKCB1 (224230), caused by mutation in the NOLA3 gene (606471) on chromosome 15q14; DKCB2 (613987), caused mutation in the NOLA2 gene (606470) on chromosome 5q35; DKCB3 (613988), caused by mutation in the TCAB1 gene (WRAP53; 612661) on chromosome 17p13; DKCB4 (see 613989), caused by mutation in the TERT gene; DKCB5 (615190), caused by mutation in the RTEL1 gene (608833) on chromosome 20q13; DKCB6 (616353), caused by mutation in the PARN gene (604212) on chromosome 16p13; and DKCB7 (see 616553), caused by mutation in the ACD gene (609377) on chromosome 16q22. X-linked recessive DKCX (305000) is caused by mutation in the dyskerin gene (DKC1; 300126) on Xq28. Hoyeraal-Hreidarsson syndrome, the severe clinical variant of DKC, can be caused by mutation in several different DKC-associated genes; see, e.g., DKC1 (300136), TINF2 (604319), TERT (187270), and RTEL1 (608833). See also adult-onset telomere-related pulmonary fibrosis and/or bone marrow failure-1 and -2 (PFBMFT1, 614742 and PFBMFT2, 614743), which are caused by mutations in the TERT and TERC genes, respectively. These disorders share some features of DKC, but show later onset and do not have skin abnormalities. The disorders related to telomere shortening are part of a phenotypic spectrum. Mutation in the CTC1 gene (613129) on chromosome 17p13 causes cerebroretinal microangiopathy with calcifications and cysts (CRMCC; 612199), another telomere-related disorder with overlapping features of DKC.

Prevalence of clinical parameters (%)