What is Dyskeratosis congenita?
Dyskeratosis congenita (DC) is a genetic disease that is typically characterized by changes in the nails and mucous membranes and pigment disorders in the neck, chest, and back areas. There is an increased risk of progressive blood formation failure and that cancer and changes in the lungs will develop. The way it manifests is variable, with some of the above symptoms often missing.
How is Dyskeratosis congenita diagnosed?
Clinical Presentation
The classic DC diagnosis triad – which is not present in all patients – is made up of the following:
Patients with DC have an increased risk of developing progressive bone marrow failure. Severe white blood cell diseases (particularly myelodysplastic syndrome and acute myeloid leukemia) and malignant mucous membrane changes in the head and neck area and the genital region frequently occur. The most common change in the lungs is called pulmonary fibrosis, which is a lung tissue alteration. Other findings are pigment changes in the skin and changes in the eyes and teeth.
Specific Clinical Findings:
Progressive Forms of Dyskeratosis Congenita
There are 2 severe progressive forms of dyskeratosis congenita, which manifest as described below:
Genetic Diagnostics
DC can be diagnosed based on its characteristic clinical presentation and confirmed by laboratory analysis. A short lymphocytic telomere length along with matching symptoms is a strong indicator for DC. In a few patients, it is also possible to prove that there is a defect in one of the many DC genes. Not all the genes involved have however been identified.
What is the risk of cancer?
The risk of a malignant disease is 11 times higher compared to the general population. The occurrence is predominantly observed starting from the 3rd decade of life.
The most common severe diseases affect the white blood cells (myeloid neoplasia: myelodysplastic syndrome, acute myeloid leukemia) and tumors of the head and neck area, gastrointestinal tract, and anogenital area (squamous epithelial carcinomas and adenocarcinomas).
What causes Dyskeratosis congenita?
Dyskeratosis congenita is a telomere disease. Telomeres are found at the end of the chromosomes that carry our genetic information and are responsible for chromosomal stability and thus for protecting our genetic information. Our stem cells are unable to divide properly when the telomeres are disrupted. A wide variety of symptoms can occur.
Is there a treatment?
Treatment predominantly consists of diagnosing preliminary cancer stages as early as possible. Treatment is in line with the corresponding treatment recommendation. Androgen therapy and a bone marrow transplant may be worth considering in cases of bone marrow failure.
Surveillance Recommendations for the Early Detection of Cancer
Surveillance Recommendations
Evidence-based standards for tumor screening and clinical management are lacking due to the rarity of the disease. The following are the recommendations from the AACR consensus meeting in October 2016:
Self-Care and Support
What should I pay special attention to?
Monthly oral self-monitoring for changes in mucous membrane
Avoid carcinogenic and noxious agents (nicotine, alcohol)
Treatment according to the manifestation