Dyskeratosis Congenita
Dyskeratosis congenita (DC) is an extremely rare, genetically inherited multi-symptom disorder (it is estimated to occur in one out of one million people worldwide). It can be characterized by a variety of symptoms including skin abnormalities, abnormal nail growth, lesions in the mucous membranes (such a leukoplakia in the mouth: white patches of potentially precancerous tissue), and in approximately 90% of the cases, progressive bone marrow failure. A variety of other abnormalities can also occur; these, as well as further detail on those listed above, are itemized in the section titled “Symptoms” (below). DC patients come from all over the world and there seems to be no bias as to race or ethnicity. The disorder does, however, appear to be much more prevalent in men than women.
Most often, the first outward symptoms of DC appear by age 10. Skin and nail abnormalities tend to present first. Bone marrow failure and other serious complications tend not to appear until the patient reaches his/her 20’s and 30’s. However, the ages at which different patients manifest different symptoms can vary greatly. The database of cases is still so limited that making generalizations is difficult.
Genetics:
DC is a genetically inherited disease. It can be inherited in one of three types: autosomal dominant, autosomal recessive, or the most common form, X-linked recessive (where the gene responsible for DC is carried on the X-chromosome). The DKC1 gene was identified in 1998 and the gene (TERC-RNA component of telomerase) mutated in autosomal dominant DC was identified in 2001. Genetic analysis can test for these genes. Because of this, family members can be tested. An infant at risk can be tested either prenatally or immediately at birth. This would allow for early treatment. Early diagnosis would also allow a patient to harvest his own bone marrow for storage for possible use in the future.
Diagnosis:
DC can be definitively diagnosed in most cases by genetic testing.
There are a couple of ways to test for it: the patient can either submit a blood sample or have his mouth swabbed for cells to be tested. Testing is available through the DKC registry (to contact them, click on this link for their e-mail address) and through a company called GeneDx. In certain cases the results of this testing have been negative even when the disease is present; in these cases, diagnosis must be made via identification of symptoms.
Symptoms:
The most typical symptoms of DC include the combination of
* skin and nail abnormalities,
* leukoplakia of the mucous membranes, and
* bone marrow failure.
Skin abnormalities can include:
* Abnormal pigmentation with hyper- (too much) or hypo- (not enough) pigmented spots and patches. This occurs in some form in about 90% of patients. The pattern typically appears on the face, neck and upper trunk and involves sun-exposed areas.
* Alopecia (balding) of the scalp, eyebrows, and eyelashes, and premature graying, hyperkeratosis (thickening and drying out) of the palms and soles, and loss of the ridges on the fingers and toes.
Nail abnormalities, which appear in approximately 90% of patients, can include:
* Ridges and vertical splitting, and
* Weakening and thinning…
usually beginning with the fingernails and then the toenails. Eventually this can lead to small or even absent nails.
Mucous Membrane Leukoplakia consist of potentially pre-cancerous white patches on the insides of the mouth and the upper throat, or possibly even other mucousal sites such as the esophagus, the genitor-urinary tract, the anus, the glans penis and the tear ducts. Patients can have an increased risk of malignancies such as squamous cell carcinomas particularly at the sites of the leuokoplakia.
Bone Marrow Failure: This most serious symptom of DC manifests in some manner in about 90% of all patients. It can first show up in any one of several ways depending on the patient: either…
* Thrombocytopenia (low platelet count — the cells needed for clotting);
* Neutropenia (low white count — the cells needed for immunity); and/or
* Anemia (low red blood count — the cells needed to carry oxygen and iron).
Of the patients who die from some DC-related condition, bone marrow failure – or some resulting ailment – is the culprit about 70% of the time. Most of the remaining 30% is accounted for by pulmonary complications and malignancies.
Lung complications: Approximately 20% of patients develop pulmonary problems such as pulmonary fibrosis. It is suggested that DC patients avoid taking any drugs with lung toxicity and that they have their lungs shielded from any radiation. This is to help protect against lung failure post bone marrow transplant.
Eyes: patients with DC have shown increased incidence of conjunctivitis and either excessive tearing or excessive dryness.
Skeletal: patients may have osteoporosis, aseptic necrosis, scoliosis, and/or mandibular hypoplasia (small jaw).
Gastrointestinal: cirrhosis, simultaneous enlargement of the liver and the spleen.
Neurologic: some patients may show signs of learning issues and mental retardation.
Genitourinary: abnormalities of the genitals or urinary tract.
Treatment:
The most devastating symptom of DC is bone marrow failure. It is often treated with either anabolic steroids (eg, oxymetholone) or bone marrow stimulating drugs such as Epogen, which stimulates the production of red blood cells, and Neupogen, which stimulates white blood cell production.
The only long-term cure is a bone marrow transplant or a stem cell transplant. These transplants have not always been so successful due to the fact that many patients have complications resulting from the pulmonary symptoms. The best candidates for this are patients with sibling donors (i.e., perfect matches) and no history of pulmonary disease. Even for “ideal” transplant candidates, however, the procedure carries a high level of risk and is usually only performed as a last resort.
Although DC is a rare disease, there is research being done by several institutions. Researchers at Johns Hopkins have been studying mice and how the lack of the protein telomerase contributes to the aging process and stem cell death. This research has major implications for DC patients. In addition, the National Cancer Institute at the National Institute of Health (NIH) in Bethesda, MD is conducting a study on genetically inherited bone marrow failure diseases, including DC.
Bibliography:
Dyskeratosis Congenita: Contact a Family--for families with disabled children.
eMedicine--Dyskeratosis Congenita: Article by David T Robles, MD
Dyskeratosis Congenita--Rare/Orphan Diseases
Disclaimer: Medicine is a constantly changing science and not all treatments are clearly established especially with such a rare disease. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this website have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. They are also not responsible for any of the statements made by individuals posting their own stories or experiences on this site.
