Dyskeratosis congenita

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 28, 2016
StartDiseasesDyskeratosis congenita

Dyskeratosis congenita is a genetic disorder in which the bone marrow does not produce enough blood cells. Dyskeratosis refers to the degeneration of skin tissue, and congenita means that the condition is congenital or present at birth. Dyskeratosis congenita accounts for approximately 1 percent of telomere syndromes, which are inherited conditions that ultimately lead to bone marrow failure.


Definition & Facts

Dyskeratosis congenita was first documented in medical literature in 1906. Initially, it was thought that the condition only affected the nails, skin, and mucous membranes of the mouth. In the 1960s, it was discovered that patients who had a combination of abnormal skin, malformed nails, and thick, white patches on the inside of their mouth would almost always develop bone marrow failure. In some patients, the skin abnormalities may develop before the failure of the bone marrow.

Some individuals with the genetic mutation that causes dyskeratosis congenita only develop a mild form of the condition, and the clinical features of the disease may not become apparent until later in life. Those with an atypical form of the disease may never develop the characteristic skin abnormalities. It is even possible for a person to have the dyskeratosis congenita mutation yet never develop the disease; however, these silent genetic carriers may still be able to pass the mutation along to their children.

Symptoms & Complaints

The severity and the timing of the onset of dyskeratosis congenita symptoms can vary widely depending on the exact nature of the genetic mutation and the number of generations in which the disease has been inherited. Except in the most severe forms of the disease, the clinical symptoms typically do not appear until later in childhood or adolescence. In some cases, the disease does not manifest until adulthood.

Patients with dyskeratosis congenita often develop abnormal skin pigmentation on sun-exposed areas of the body. The areas may be dark, gray, or light colored and are normally distributed in a net-like pattern. Leukoplakia, which are thick, white patches, may develop on the inside of the mouth. The nails of the toes and fingers may be underdeveloped, have fissures, or even degenerate completely.

Almost all individuals with dyskeratosis congenita ultimately develop bone marrow failure resulting in a deficiency of white blood cells, red blood cells, and platelets. This can lead to a number of symptoms, including anemia, frequent infections, and frequent or excessive bruising and bleeding.

Individuals with the disease are also predisposed to developing leukemia and malignant tumor, especially cancers of the skin. Patients who develop the condition later in life often develop pulmonary fibrosis, which causes decreased lung function and difficulty breathing.


Six different gene mutations have been identified as causing dyskeratosis congenita. One mutation involves the X chromosome. Females are born with two X chromosomes; however, one is inactivated. Females can be carriers of X-linked dyskeratosis congenita, but they normally will not develop symptoms since it is typically the abnormal X chromosome that is inactivated. Since males only have one X chromosome, they will develop the disease.

Mutations involving chromosomes 3, 5, and 14 account for some instances of autosomal dominant dyskeratosis congenita. An autosomal dominant defect only requires one copy of the mutated gene to be inherited for the disease to occur. Either parent can pass along the mutation, and each child has a 50 percent chance of inheriting the mutation.

Mutations on chromosomes 5 and 15 can also result in autosomal recessive dyskeratosis congenita. To develop the disease, the child must inherit a mutated gene from each parent. Children who inherit only one defective gene are carriers but normally do not develop the disease. With autosomal recessive dyskeratosis congenita, the risk of having a child who is a carrier is 50 percent with each pregnancy. The risk of having an affected child is 25 percent. In a significant number of patients with dyskeratosis congenita, the mutation occurs spontaneously

Diagnosis & Tests

Changes in the skin and mucous membranes of the mouth will often lead a doctor to suspect that a patient has dyskeratosis congenita. The diagnosis can be more difficult in individuals who develop bone marrow failure or pulmonary fibrosis without the characteristic skin abnormalities. Blood tests will typically show low levels of all three types of blood cells.

The ends of the peripheral blood cells, called telomeres, will also be shortened in individuals with bone marrow failure. The telomeres are meant to protect the chromosome from damage similar to the way the plastic tips on shoelaces prevent the lace from fraying. When the telomeres are shortened, the cell can stop growing or die.

Children with dyskeratosis congenita must be monitored closely and undergo frequent blood tests to monitor for bone marrow failure or leukemia. Pulmonary function tests can be used to measure the function of the lungs and identify possible pulmonary fibrosis. 

Treatment & Therapy

The goal of treatment is to manage the symptoms and to cure the bone marrow failure and any cancers that may arise. Individuals diagnosed with dyskeratosis congenita should avoid smoking and alcohol to prevent damaging the lungs and liver.

Skin issues may be treated using moisturizing creams. It is important for individuals with the condition to practice good oral care and to see a dentist regularly to prevent tooth loss and to detect possible oral cancers.

Androgens, corticosteroids, and hematopoietic growth factors may be used to increase blood cell levels; however, their effectiveness is usually only temporary. The only possible cure for bone marrow failure is a stem cell or bone marrow transplant in which the patient’s stem cells or bone marrow are replaced with those of a healthy donor. Patients who develop lung disease or liver disease may ultimately require an organ transplant

Prevention & Prophylaxis

Since dyskeratosis is a genetic condition, there is nothing that can be done to prevent the disease. A test called flow-FISH may be used to screen for silent and clinically apparent forms of the disease. This can help individuals who may be carriers of the disease make informed decisions regarding having children.

Since dyskeratosis can affect multiple systems, the prognosis is generally poor. A large number of patients die during adolescence or early adulthood. Most deaths are attributed to malignancy or infections or bleeding related to bone marrow failure.