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:

  • Changes in the nails (growth and nutritional disturbances in fingernails and toenails)

  • Changes in the mucous membrane, with extensive whitish patches (oral leukoplakia)

  • Pigment disorders in the neck, chest, and back areas

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 bone marrow failure with blood production disorders: thrombopenia, leukopenia, anemia (50% up to the age of 40)

  • Changes in the lungs, primarily pulmonary fibrosis (65%)

  • Changes in the liver

  • Changes in the skin and nails

  • Growth and developmental delay (dwarfism)

  • Eyes: epiphora, abnormal eyelash growth, retinal diseases affecting both eyes

  • ENT: extensive whitish changes in the mucous membranes (oral leukoplakia), deafness (rare)

  • Cardiovascular: heart defects and myocardial diseases

  • Gastrointestinal tract: for example, constriction of the esophagus, pathological mucous membrane changes throughout the entire gastrointestinal tract

  • Urogenital tract: constriction of the urethra (urethral stenosis)

  • Musculoskeletal system: reduction in bone density, bone circulation disorder in the shoulder and hip

  • Psychiatry: schizophrenia

  • Hormonal balance: gonadal dysfunction (hypogonadism)

  • Immunology: immune deficiency

Progressive Forms of Dyskeratosis Congenita

There are 2 severe progressive forms of dyskeratosis congenita, which manifest as described below:

  • Hoyeraal-Hreidarsson syndrome: early childhood onset; the classic DC features plus underdevelopment of the cerebellum, developmental retardation, immunodeficiency, prenatal growth delay, bone marrow failure

  • Revesz syndrome: early childhood onset; in addition to the features of DC, retinal disease, calcifications in the central nervous system, prenatal growth delays, bone marrow failure, sparse and thin hair, changes in the nails, changes in the mucous membranes

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:

  • Hematology-oncology: annual blood count, annual bone marrow puncture and punch biopsy if corresponding clinical symptoms have been diagnosed, early referral to a transplant center, HPV vaccination, annual ENT checkups from adolescence (early tumor detection)

  • Immunology: monitoring immunoglobulins according to immunological recommendations

  • Dermatology: annual skin examination

  • Pulmonology: function testing with regular progression checks following the diagnosis

  • Gastroenterology: annual liver function test, more frequently with concomitant androgen therapy (six-monthly ultrasound of the liver, three-monthly liver function tests)

  • Endocrinology: annual diabetes test, growth monitoring

  • Neurology: MRI of the head at the time of diagnosis, early assistance when there is developmental delay

  • Eyes: annual examinations, monitoring, and early treatment in the event of lacrimal duct stenosis

  • Orthopedics: examination of the hip and shoulder depending on the clinical symptoms (aseptic bone necrosis)

  • Dental: six-monthly checkups

  • ENT: hearing status at the time of diagnosis

  • Cardiology: examination to check for malformations at the time of diagnosis

  • Urogenital tract: examination to check for urogenital malformations at the time of diagnosis

  • Gynecology: annual examination

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

Support Groups and Additional Information