Information on the following diseases can be found in the Related Disorders section of this report:

• Ectodermal Dysplasias
• Fanconi's Anemia

The main symptoms of Dyskeratosis Congenita are:

1. Hyper and Hypopigmentation - Hyperpigmentation in Dyskeratosis Congenita has a net like pattern of distribution that is brownish-grey in color. Hypopigmentation is a lack of skin color that is intermixed. These skin discolorations may be present at birth but usually are progressive and appear later.

2. Progressive nail dystrophy may lead to loss of nails on the fingers or toes. This is visually not present at birth.

3. Mucosal leukoplakia - a slowly developing change in normal tissue of a mucous membrane. This condition may be found in the mucous membranes of the anus, urethra, lips, mouth and/or eyes. This condition should be watched closely and the leukoplakic lesions removed before they can become malignant.

The following conditions are often, but not always, present in patients with Dyskeratosis Congenita:

4. Pancytopenia - a reduction in the normal number of red and white blood cells and platelets caused by bone marrow failure.

5. Hyperkeratosis - the overgrowth of skin on the palms of the hands and the soles of the feet. This condition often causes a lack of finger and foot prints.

6. Hyperhidrosis - excessive sweating of the palms of the hands and the soles of the feet.

7. Atresia of the lacrimal puncta - absence of the tiny opening in the edge of each eyelid that drains the tears. This condition causes chronic tearing.

The following conditions are sometimes associated with Dyskeratosis Congenita and have been found in some patients with this disorder:

8. Alopecia - absence of hair from skin areas where it is normally present. The hair is often fine and sparse and there may be premature graying.

9. Dental abnormalities - displacement of teeth from a normal position in the dental arch. Teeth may also be lost at an early age.

10. Osteoporosis - a decrease in bone mass. Patients with Dyskeratosis Congenita may also have a fragile build and a slow growth pattern.

11. Testicular atrophy - incomplete or underdeveloped testes. The penis may also be underdeveloped.

12. Thrombocytopenia - an abnormally small number of platelets (the part of the blood that helps in clotting) in the circulating blood.

13. Microcephaly - a small circumference of the head.

14. Mental retardation or reduced intelligence.

15. Cirrhosis of the liver - a long-term disease of the liver in which the liver becomes covered with fiberlike tissue and hardens - also called nutmeg-like cirrhosis.

16. Dysphasia - difficulty in swallowing.

17. Acrocyanosis - hands and/or feet that are a blue color, cold and sweaty. This is caused by spasms of the blood vessels and usually occurs when the patient is cold or under stress.

18. Cataracts - a disease of the eye in which the lens loses it's clearness. A grey-white film can be seen in the lens. (For more information on this disorder choose "Cataracts" as your search term in the Rare Disease Database).

Most cases of Dyskeratosis Congenita have an X-linked recessive inheritance although cases have been reported of autosomal recessive and autosomal dominant inheritance. A significant number of cases have also occurred sporadically.

Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

X-linked recessive disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons.

Dyskeratosis Congenita has been mapped to the Xq27-q28 gene.

Dyskeratosis Congenita affects males most often, with the ratio of affected males to females being M10:F1. This disorder is usually detected between the ages of five and fifteen although skin and nail abnormalities may be present at birth. There have been only 120 cases of Dyskeratosis Congenita reported and the disease has occurred in all races.

Symptoms of the following disorders can be similar to those of Dyskeratosis Congenita. Comparisons may be useful for a differential diagnosis:

Ectodermal Dysplasias are a group of hereditary, non-progressive syndromes in which the affected tissue derives primarily from the ectodermal germ layer. The skin, it's derivatives, and some other organs are involved. A predisposition to respiratory infections, due to a somewhat depressed immune system and to defective mucous glands in parts of the respiratory tract, is the most life threatening characteristic of this group of disorders. Symptoms include eczema, poorly functioning sweat glands, sparse or absent hair follicles, abnormal hair, disfigured nails, and difficulties with the nasal passages and ear canals. Skin is satiny smooth, prone to rashes, and slow to heal. (For more information on this disorder choose "Ectodermal Dysplasias" as your search term in the Rare Disease Database.)

Fanconi's Anemia is a rare form of familial aplastic anemia (a disease of the bone marrow) found chiefly in children. It is characterized by bone marrow abnormalities, a small circumference of the head, retarded sexual development and brown pigmentation of the skin. Complications such as pneumonia and meningitis, hemorrhages and leukemia may occur. (For more information on this disorder choose "Anemia, Fanconi's" as your search term in the Rare Disease Database.)

Treatment of Dyskeratosis Congenita is symptomatic and supportive. Leukoplakic lesions should be surgically removed to prevent malignancy. Dental abnormalities will require dental intervention.

Genetic counseling may be of benefit for patients and their families.

Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future.

McKusick VA., ed. Online Mendelian Inheritance in Man. Baltimore, MD: The Johns Hopkins University Press; Entry No: 305000; Creation date: 6/3/86; Last Update for X-linked form: 12/1/99; Last Update for autosomal recessive form: 3/12/99.

TEXTBOOKS
Jones KL., ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Co; 1997:538-39.

Buyse ML. ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, For: Center for Birth Defects Information Services Inc; 1990:567-68.

Esterly NB. Dermatologic disorders. In: Thoene JG., ed. Physicians’ Guide to Rare Diseases. Montvale, NJ: Dowden Publishing Company Inc; 1995:618-19.

REVIEW ARTICLES
Dokal I. Dyskeratosis congenita. Br J Haematol. 1999;105 Suppl 1:11-15

Solder B, et al., Dyskeratosis congenita: multisystemic disorder with special consideration of immunologic aspects. A review of the literature. Clin Pediatr (Phila). 1998;37:521-30.

JOURNAL ARTICLES
Knight SW, et al., Unexplained aplastic anemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1. Br J Haematol. 1999;107:335-39.

Dokal I. Dyskeratosis congenita: recent advances and future directions. J Pediatr Hematol Oncol. 1999;21:344-50.

Knight SW, et al., X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. Am J Hum Genet. 1999;65:50-58.

Ghavamzadeh A, et al., Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation. Bone Marrow Transplant. 1999;23:299-301.