Dyskeratosis congenita (DKC) is an inherited disorder. Symptoms include abnormal skin pigmentation, abnormal nail growth, and leukoplakia (white patches inside the mouth). Patients with DKC are predisposed to bone marrow failure, some cancers, and pulmonary problems. A registry was established in 1995 to study the clinical features of this disease.
Symptoms typically surface between the ages of five and 10 years, although diagnosis has occurred in infants and well into adulthood. Symptoms and their severity vary widely from patient to patient. Those patients who experienced bone marrow failure, malignancies, or pulmonary complications accounted for the majority of deaths from this disorder.
Symptoms of DKC may include skin rash in a spotted or lacey pattern, usually on the upper part of the body, neck, and face; ridges and fissures in the nails that become weakened, thin, and distorted or nails that become very thin and even disappear; white patches (leukoplakia) on the insides of the cheeks, tongue, and upper throat . Many patients with DKC lack some or all of these symptoms.
If they develop, the onset of symptoms is progressive and appears between five and 10 years of age. The progression varies from person to person. About 20 percent of patients experience pulmonary disease (like pulmonary fibrosis) and complications from pulmonary disease may be life-threatening.
Other symptoms include hair loss, tooth abnormalities, and problems with the lungs or digestive system. A weakened immune system may lead to infections and possibly cancer. Learning difficulties, mild-to-moderate developmental delay, or short stature may be seen in some patients. Low bone density increases the risk of fractures.
There is an increased risk of developing cancers (both leukemias and solid tumors) compared with the general population, and so the risk increases in older patients, usually over 20 years of age.
DKC patients show poor blood cell production by the bone marrow. The defect lies with the stem cells. When a patient experiences bone marrow failure, the bone marrow fails to produce enough white or red blood cells, or platelets.
In people with DKC, the skin, nail and mucous membrane symptoms usually appear between age five and ten. Bone marrow failure may begin in childhood as well. Genetic testing can identify the gene mutation when it is known that family members have this disorder. The telomeres are typically very short in patients with DKC.
There are three types of DKC: X-linked, autosomal dominant, and autosomal recessive. Each is associated with different sets of genes. Many patients with DKC have no mutations in these genes – so there are likely additional as yet unidentified genes.
X-linked DKC is caused by a mutation to the DKC1 gene, located on the X chromosome, and in most cases is inherited as an X-linked recessive disorder. This form of DKC affects mostly male patients. Autosomal dominant DKC is caused by mutations in the TERC, TERT, and TINF2 genes.
Autosomal recessive DKC is caused by mutations in the NOP10 and NHP2 genes. Mutations in TERT may also cause an autosomal recessive variant of DKC.