$Unique_ID{BRK03680} $Pretitle{} $Title{Dyskeratosis Congenita} $Subject{Dyskeratosis Congenita DKC Dyschromatosis Universalis Hereditaria Dyskeratosis Congenita Autosomal Recessive Type Dyskeratosis Congenita Scoggins Type Dyskeratosis Congenita Syndrome Zinsser-Cole-Engman Syndrome Ectodermal Dysplasias Fanconi's Anemia} $Volume{} $Log{} Copyright (C) 1992 National Organization for Rare Disorders, Inc. 896: Dyskeratosis Congenita ** IMPORTANT ** It is possible that the main title of the article (Dyskeratosis Congenita) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms DKC Dyschromatosis Universalis Hereditaria Dyskeratosis Congenita, Autosomal Recessive Type Dyskeratosis Congenita, Scoggins Type Dyskeratosis Congenita Syndrome Zinsser-Cole-Engman Syndrome Information on the following diseases can be found in the Related Disorders section of this report: Ectodermal Dysplasias Fanconi's Anemia General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Dyskeratosis Congenita is a rare disorder in which three groups of symptoms occur: darkening and/or unusual absence of skin color (hyper/hypopigmentation); progressive nail dystrophy; and slowly changing characteristics of mucous membranes (leukoplakia) in the anus, urethra, lips, mouth and/or eye. Other symptoms found in some patients with this syndrome may be reduction in red and white blood cells and platelets (pancytopenia), overgrowth of skin on the palms of the hands and soles of the feet, excessive sweating of the palms and soles, sparse or absent hair, fragile bones, underdeveloped testes, and dental abnormalities. Dyskeratosis Congenita is more prevalent among males then females and an X-linked recessive inheritance is the most common form although cases of autosomal recessive and autosomal dominant inheritance have been recorded. This disorder has also occurred sporadically (no known cause) in a significant number of cases. Symptoms 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). Causes 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 fifty 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 one 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 twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal. X-linked recessive disorders are conditions which 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 fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. Dyskeratosis Congenita has been mapped to the Xq27-q28 gene. Affected Population 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. Related Disorders 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). Therapies: Standard 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. Therapies: Investigational 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. This disease entry is based upon medical information available through February 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Dyskeratosis Congenita, please contact: National Organization for Rare Disorders P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 National Foundation for Ectodermal Dysplasias 219 E. Main St. Mascoutah, IL 62258 (618) 566-2020 NIH/National Institute of Child Health and Human Development (NICHD) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5133 NIH/National Heart, Lung and Blood Institute (NHLBI) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-4236 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 275, 1154, 1586. SMITH'S RECOGNIZABLE PATTERNS OF HUMAN MALFORMATION, 4th Ed.: Kenneth L. Jones, M.D., Editor; W.B. Saunders Co., 1988. Pp. 474. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 567-68. DIAGNOSTIC RECOGNITION OF GENETIC DISEASES, William Nyhan, Nadia O Sakati, Editors; Lea & Febiger, 1987. Pp. 600, 672. ENHANCED G2 CHROMATID RADIOSENSITIVITY TO DYSKERATOSIS CONGENITA FIBROBLASTS: D.M. DeBauche, et al.; Am J Hum Genet (February, 1990, issue 46(2)). Pp. 350-7. DYSKERATOSIS CONGENITA: REPORT OF A CASE AND REVIEW OF THE LITERATURE: G.R. Ogden, et al.; Oral Surg Oral Med Oral Pathol (May 1988, issue 65(5)). Pp. 586-91. ETIOLOGIC HETEROGENEITY IN DYSKERATOSIS CONGENITA: G.S. Pai, et al.; Am J Med Genet (January 1989, issue 32(1)). Pp. 63-6.