$Unique_ID{BRK03876} $Pretitle{} $Title{Ichthyosis, X-Linked} $Subject{Ichthyosis, X-Linked Steroid Sulfatase Deficiency DOC 2 Disorder of Cornification 2 Ichthyosis Ichthyosis Congenita Ichthyosis Vulgaris } $Volume{} $Log{} Copyright (C) 1988, 1989, 1991, 1992, 1993 National Organization for Rare Disorders, Inc. 545: Ichthyosis, X-Linked ** IMPORTANT ** It is possible the main title of the article (X-Linked Ichthyosis) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names and disorder subdivisions covered by this article. Synonyms Steroid Sulfatase Deficiency DOC 2 Disorder of Cornification 2 Information on the following disorders can be found in the Related Disorders section of this report: Ichthyosis Ichthyosis Congenita Ichthyosis Vulgaris 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. X-Linked Ichthyosis is a genetic skin disorder that affects males. It is an inborn error of metabolism characterized by a deficiency of the enzyme steroid sulfatase. This enzyme defect leads to several biochemical alterations in the steroid sex hormone metabolism, including diminished maternal estrogen production in late pregnancy. Cholesterol sulfate may accumulate in the blood and skin. Normal functioning of sex hormones does not appear to be affected. Corneal opacities may be present, but do not interfere with vision. Symptoms Symptoms of X-Linked Ichthyosis usually begin between 1 and 3 weeks of age. The disorder is characterized by the development of brownish scales (ichthyosis) that usually adhere tightly to the underlying skin. Scales are most prominent on the skin covering muscles, especially areas on one side of the limbs (extensor muscles). The scales may spread to the surfaces where the flexing muscles are located. However, the skin in the hollow of the elbows and knees is usually affected less often than the back of the neck, which is almost always scaly. The face and scalp are usually free of scales, but the trunk is often involved. Palms of the hands and soles of the feet are almost always spared. Marked improvement of symptoms often occurs during the summer. When they are giving birth to a male fetus who has X-Linked Ichthyosis, women who are carriers of the disorder often experience a delay in labor and sometimes difficulties with cervical dilatation. Diminished estrogen production often develops among female carriers when they are pregnant with a male fetus who has this disorder. Clouding of the eye's cornea may occur in about half of the men with X- Linked Ichthyosis during adulthood. Failure of the testicles to descend into the scrotum may occur in approximately 12 to 25% of patients with X-Linked Ichthyosis. Additionally, these patients may be at increased risk to contract malignancies of the testicles. Causes X-Linked Ichthyosis is a hereditary disorder transmitted by sex-linked genes. Symptoms are caused by a deficiency of the enzyme steroid sulfatase. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. 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 have only 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.) Affected Population X-Linked Ichthyosis is a rare disorder affecting one in 2,000 males. This means there are 500 cases per million with 62,500 persons affected in the United States, and occuring in about 1,865 births yearly. Female carriers may transmit the disorder without having any symptoms themselves. Related Disorders Symptoms of the following disorders may be similar to those of X-Linked Ichthyosis. Comparisons can be useful for a differential diagnosis: "Ichthyoses" or "Disorders of Cornification" are general terms describing a group of scaly skin disorders. They are characterized by an abnormal accumulation of large amounts of dead skin cells (squames) in the top layer of the skin. The conversion of an abnormally large number of epidermal cells into squamous cells is thought to be caused by a defect in the metabolism of the skin cells known as "corneocytes" or of the fat-rich matrix around these cells. The cells can be thought of as bricks, while the matrix would be the mortar holding these cells together. (See "Ichthyosis" in the Rare Disease Database.) Ichthyosis Congenita (Collodion Baby; Congenital Ichthyosiform Erythroderma; Xeroderma; Desquamation of Newborn) is an inherited skin disorder. It is characterized by generalized, abnormally red, dry and rough skin, with large, coarse scales. Itchiness (pruritus) usually also develops. Skin on the palms of the hands and soles of the feet is abnormally thick. (For more information, choose "Ichthyosis Congenita" as your search term in the Rare Disease Database.) Other forms of Ichthyosis include Sjogren-Larsson Syndrome, Netherton Syndrome, Ichthyosis Hystrix, Lamellar Ichthyosis, Refsum Syndrome, Darier Disease, Conradi-Hunermann Syndrome, Chanarin-Dorfman Syndrome, Epidermolytic Hyperkeratosis, etc. (Search under each name for more information on that disorder in the Rare Disease Database.) Therapies: Standard X-Linked Ichthyosis can be diagnosed before birth by taking a few cells from the fluid in the water sac that surrounds the fetus and testing these for abnormalities. This test is called amniocentesis. X-Linked Ichthyosis is treated by applying skin softening (emollient) ointments, preferably plain petroleum jelly. This can be especially effective after bathing while the skin is still moist. Salicylic acid gel is another particularly effective ointment. The skin should be covered at night with an airtight, waterproof dressing when this ointment is used. Lactate lotion can also be an effective treatment for this disorder. Therapies: Investigational Drugs derived from Vitamin A (retinoids) such as tretinoin, motretinide, and etretinate are often effective against X-Linked Ichthyosis, but can cause toxic effects on the bones in some cases. A synthetic derivative of Vitamin A, isotretinoin, when taken by pregnant women, can cause severe birth defects to the fetus. These Vitamin A compounds have not yet been approved by the Food and Drug Administration (FDA) for treatment of Ichthyosis. The National Institute of Arthritis, Musculoskeletal and Skin Diseases is looking for patients with various kinds of Ichthyosis willing to participate in research aimed at mapping the genes responsible for their disorder. Interested persons may contact: Dr. Sherri Bale National Institute of Arthritis, Musculoskeletal and Skin Diseases 9000 Rockville Pike Bethesda, MD 20892 (301) 402-2679 The orphan product Monolaurin (Glylorin) is being tested for the treatment of X-Linked Ichthyosis. The product is manufactured by: Cellegy Pharmaceuticals, Inc. 371 Bel Marin Keys, Suite 210 Novato, CA 94949 This disease entry is based upon medical information available through May 1993. 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 X-Linked Recessive Ichthyosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Foundation for Ichthyosis and Related Skin Types, Inc. (F.I.R.S.T.) P.O. Box 20921 Raleigh, NC 27619-0921 (919) 782-5728 (800) 545-3286 The National Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse Box AMS Bethesda, MD 20892 (301) 495-4484 For genetic information and genetic counseling referrals, please contact: 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 GENETICALLY TRANSMITTED, GENERALIZED DISORDERS OF CORNIFICATION. THE ICHTHYOSES: M.L. Williams, et al.; Dermatol Clin (January 1987: issue 5(1)). Pp. 155-178. THERAPEUTIC ACTIVITY OF LACTATE 12% LOTION IN THE TREATMENT OF ICHTHYOSIS. ACTIVE VERSUS VEHICLE AND ACTIVE VERSUS A PETROLEUM CREAM: M. Buxman, et al.; Journal Am Acad Dermatol (December 1986: issue 15(6)). Pp. 1253-1258. THE METABOLIC BASIS OF INHERITED DISEASE, 5th ed.: John B. Stanbury, et al., eds.; McGraw Hill, 1983. Pp. 1027-1039. TOPICAL CHOLESTEROL TREATMENT OF RECESSIVE X-LINKED ICHTHYOSIS: G Lykkesfeldt, et al.; Lancet (December 10, 1983: issue 2(8363)). Pp. 1337- 1338.