Dyskeratosis congenita has a wide phenotypic spectrum and age onset. It usually manifests during childhood with the triad of dysplastic nails, lacy reticular pigmentation and atrophy of the skin at the level of the neck and upper chest, and oral leukoplakia. Patients show an increased risk for progressive BMF and may develop myelodysplastic syndrome or acute myelogenous leukemia (see these terms) at any age (the risk increasing with age). There is also an increased risk for solid tumors, typically squamous cell carcinoma of head and neck or anogenital cancer. Various additional clinical findings have been reported and may include: developmental delay, short stature, microcephaly, blepharitis, epiphora, periodontal disease, taurodontism, decreased teeth/root ratio, esophageal stenosis, liver disease, urethral stenosis, osteoporosis, avascular necrosis of femur and/or humerus, premature hair greying/alopecia, or abnormal eyelashes. Individuals with DC are at high risk of pulmonary fibrosis.
Dyskeratosis congenita is caused by mutations in the CTC1 (17p13.1),DKC1 (Xq28),TERC (3q26.2), TERT (5p15.33), TINF2 (14q12), NHP2 (5q35.3), NOP10 (15q14-q15), RTEL1 (20q13.3), or WRAP53 (17p13.1) genes which code for proteins involved in telomere maintenance and affecting telomere length. The USB1 gene (16q13) is also involved but it is not known to be related to telomere biology. Clinical phenotypic outcome depends on the gene mutated, its penetrance and expressivity. Patients with Hoyeraal Hreidarsson syndrome, a clinically severe variant of DC, may have mutations in RTEL1, DKC1, TERTor TINF2, and patients with Revesz syndrome (see these terms), another DC variant, have mutations in TINF2.
