Dyskeratosis congenita is a genodermatosis characterized by the triad of hyperpigmentation of the skin, dystrophy of the nails, leukoplakia of mucous membranes, and in addition the presence of progressive pancytopenia. It has a highly variable phenotype.
Zinsser-Cole-Engman Syndrome; Dyskeratosis Congenita Scoggins type.
The exact incidence remains unknown, especially due to its highly variable phenotype. Thus far, approximately 200 cases have been described. It is suspected that the disease is more frequent but not diagnosed.
It is an X-linked recessive disorder that affects almost exclusively males (male-to-female ratio = 10:1). However, there are rare case reports of autosomal recessive and autosomal dominant inheritance. The mutant gene has been mapped to Xq28 and encodes for a 514-amino-acid protein called dyskerin.
Dyskerin seems to have a major role in the regulation of cell proliferation (biogenesis of ribosomes and pseudouridylation of recombinant RNA messengers) and therefore primarily affects rapidly proliferating tissues (eg, skin, gastrointestinal mucosa, and bone marrow).
The phenotype is highly variable; however, bone marrow failure and the triad of reticulated hypopigmentation and hyperpigmentation of the skin, nail dystrophy, and mucocutaneous leukoplakia is typical for dyskeratosis congenita. The onset of skin and nail changes usually is around age 10 years and precedes epiphora and mucocutaneous changes. Although signs of bone marrow failure and malignancy begin to develop in the early to mid-teens, manifestation before age 10 years is not uncommon.
Changes in skin pigmentation (reticulated hypopigmentation and hyperpigmentation) often in combination with telangiectases are more pronounced on the flexures of the big joints, neck, and axillae, and along the inner thigh. Nail dystrophy is progressive and initially may result in longitudinal ridges and finally in complete loss of nails. The hair may be affected, leading to baldness. Leukoplakia most often occurs in the mouth but also may affect other mucosal sites (eg, esophagus, vagina, anus, urethral meatus, and lacrimal duct resulting in strictures with dysphagia, dyspareunia, dysuria, and epiphora) and is associated with an increased risk for malignancies (most often squamous cell carcinoma). In male patients, testes often are undescended and hypoplastic. Dental abnormalities (extensive cavities, premature loss) and increased fragility of the bones caused by abnormal metaphyseal trabeculation and osteoporosis have been reported. Lacrimal duct stenosis or atresia is present in up to 80% of patients and leads to continuous epiphora. Up to 90% of patients suffer from bone marrow failure; rarely the diagnosis of aplastic anemia precedes the diagnosis of dyskeratosis congenita. Some patients develop myelodysplasia and acute myeloid leukemia. Pancytopenia or complications related to bone marrow transplant (high rate of pulmonary complications) are responsible for approximately 70% of the premature deaths in this population. Approximately 20% of these patients show ...