Dyskeratosis congenita is a genetic condition that affects many parts of the body. The three main characteristics of this condition include:

• Leukoplakia or whitish discoloration of the mucous membranes
• Dystrophy or abnormality of the nails
• Skin pigmentation

Inheritance

In most cases, dyskeratosis congenita is inherited in an X-linked recessive manner. This means that the gene mutation that causes the condition is located on the X chromosome. In males, the mutation would only need to occur on the one X chromosome they possess, while in females the mutation would need to occur on both of their X chromosomes. Since it is unlikely that women will inherit two mutated copies of this gene, males are affected by this condition much more frequently than women.

Pathology of dyskeratosis congenita

The exact pathology and cause of this condition is not yet fully understood. However, in about 50% of sufferers, the condition is known to be caused by mutations in the TERT, TERC, DKC1 or TINF2 genes. These genes code for important proteins that maintain telomeres, structures that are found at the ends of chromosomes. In the other 50% of sufferers, no gene mutations have yet been identified and the cause remains unknown, although researchers suspect that other genes involved in telomere maintenance may be involved.

Telomeres help prevent chromosomes from fusing together or degrading. They also induce apoptosis (programmed cell death) after a cell has divided a certain number of times and has become “worn out.” The gene mutations mentioned lead to the disruption of telomere maintenance, which causes the telomeres to become shorter. Groups of cells that undergo rapid cell division are particularly vulnerable to the effects of shortened telomeres and people with dyskeratosis congenita suffer from a range of problems affecting tissues such as the skin, hair follicles, nail beds, oral mucosa and bone marrow. Instability of the chromosomes arising form poor telomere maintenance can also lead to the uncontrolled division of cells, which raises the risk of cancer developing.

Diagnosis and treatment

Early diagnosis of dyskeratosis congenita is important to increase the chance of treatment working. In most cases, the child’s medical history will be evaluated in detail and a physical examination performed to check for signs of the condition. One or more of the following tests may then be arranged:

• Blood tests to check the blood cell counts
• Blood or saliva testing to check for genetic mutations in the genes associated with dyskeratosis congenita
• Blood tests to check whether the telomeres are shortened

The main aims of treatment are two-fold: to manage the health complications caused by the condition and to cure any bone marrow problems or cancer. Examples of medications that may be used to treat bone marrow failure include an anabolic steroid such as oxymetholone and a granulocyte colony-stimulating factor (G-CSF) such as filgrastim. However, the only cure for bone marrow failure is hematopoietic stem cell transplantation. The other complications of the condition such as lung and digestive tract disorders cannot be cured and require long-term monitoring and management to help improve the patient’s quality of life.