Dyskeratosis Congenita

Dyskeratosis congenita (DC) is a rare, inherited multi-system disorder.  It is estimated to occur in one out of one million people worldwide.  DC is characterized by abnormal fingernails and toenails, a lacey rash of the neck and upper chest and white patches on the inside of the mouth (oral leukoplakia).  In addition people with DC have an extremely high risk of progressive bone marrow failure (aplastic anemia), myelodysplastic syndrome, leukemia, and solid tumors.

The age at which patients with Dyskeratosis Congenita manifest symptoms is highly varied.  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 later. However, in some cases severe bone marrow failure may precede the physical findings.

Dyskeratosis Congenita patients come from all over the world and there seems to be no bias as to race or ethnicity.  The disorder does appear to be more frequent in men than in women.

Signs and Symptoms of Dyskeratosis Congentia

Common Clinical Findings

• Abnormal Fingernails and Toenails: ridges, splitting, wrinkled, soft, poor nail growth, often leads to absence of nails.

• Lacey, Reticular Pigmentation of the Neck and Chest: too much or too little pigmentation or patches typically occurring on the neck and upper trunk

• Oral Leukoplakia: white patches in the inside of the mouth and tongue

• Bone Marrow Abnormalities: aplastic anemia, myelodysplastic syndrome and leukemia

Less Common Findings

• Tear duct abnormalities: watery eyes or dry eyes
• Dryness of upper and lower eyelids: blepharitis (eyelid infection)
• Developmental Delay
• Short Stature
• Early Gray Hair
• Early Hair Loss
• Sparse Eyelashes
• Dental Cavities or Periodontal (gum) Disease
• Excessive Sweating: hyperhidrosis
• Narrowing of the Esophagus: esophageal stenosis
• Narrowing of the Urethra: urethral stenosis
• Lung Disease: pulmonary fibrosis
• Liver Disease: fibrosis
• Poorly Developed Cerebellum: cerebellar hypoplasia, problems with coordination
• Microcephaly: extremely small head
• Hypogonadism: poorly developed genitals in males
• Mandibular hypoplasia: extremely small jaw
• Osteoporosis
• Avascular Necrosis of the Hips or Shoulders
• Head and Neck Cancer

Genetics

Dyskeratosis Congenita is an inherited disease.  An abnormal gene (mutated) has been identified in less than half of patients with DC.  Family studies of DC show all forms of inheritance.

• X-linked: only present in males, due to a mutation in the DKC1 gene
• Autosomal Dominant: One copy of an abnormal gene is sufficient to cause disease.  Mutations in TERC and TERT have been found in DC patients to be inherited in an autosomal dominant manner.
• Autosomal Recessive:  Two copies of an abnormal gene are needed to cause disease (i.e. one from each parent).  Genes have not yet been identified in this form of DC.

Diagnosis

The diagnosis of Dyskeratosis Congenita is typically made based on the signs and symptoms described above. A patient who fits the clinical definition of DC may have genetic testing done to determine the type of mutation present. However, less than half of DC patients have a mutation in a known gene.

A sample for genetic testing can be sent by your physician after you/your family has received appropriate genetic counseling.  Typically it can be done on a blood sample or a swab of the inside of the cheek.

Treatment

The most devastating symptom of Dyskeratosis Congenita is bone marrow failure (aplastic anemia).  It is often treated with either anabolic steroids (eg, Anadrol [oxymetholone]) or bone marrow stimulating drugs such as Epogen (erythropoietin), which stimulates the production of red blood cells, and Neupogen (granulocyte-colony stimulating factor, G-CSF), which stimulates white blood cell production. 

Bone marrow or stem cell transplantation for Dyskeratosis Congenita can cure the bone marrow disease, but not the other complications of DC.  These transplants are complicated by an increased risk of lung and liver complications due to underlying abnormalities of these organs in DC. The best candidates for bone marrow or stem cell transplantation 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.

Ongoing Research and Bibliography

Related Diseases and Links

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 other treatment options almost 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.