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

• Ichthyosis
• Ichthyosis congenita
• X-Linked ichthyosis

Ichthyosis hystrix, Curth-Macklin type is characterized by patches of abnormally thick, hard skin that may appear almost anywhere on the body. Some clinicians describe the skin as "horn-like". With treatment, the patches may be considerably reduced. Under examination by electron microscopy, numerous cells (keratinocytes) with two nuclei are found. Frequently, the nuclei are surrounded by shells of a primitive, precursor protein of the skin.

The cause of ichthyosis hystrix, Curth Macklin type is a defect in the development of the precursor, structural protein (tonofilaments). The defect occurs as a result of a change (mutation) in the gene that produces (codes for) these proteins. The faulty gene has been mapped to chromosome 12q13.

Ichthyosis Hystrix, Curth-Macklin type is an inherited disorder, transmitted as an autosomal dominant trait.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 12q13" refers to band 13 on the long arm of chromosome 12. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

Ichthyosis hystrix, Curth Macklin type is a rare disorder present at birth. It affects males and females in equal numbers.

Symptoms of the following disorders may be similar to those of Ichthyosis hystrix, Curth Macklin type. 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.)

Lamellar ichthyosis is an inherited skin disorder 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, Lamellar" as your search term in the Rare Disease Database.)

X-Linked ichthyosis is an inherited skin disorder caused by a deficiency of the enzyme steroid sulfatase. This enzyme deficiency leads to biochemical alterations in the steroid sex hormone metabolism. Cholesterol sulfate may accumulate in the blood and skin. (For more information, choose "X-Linked Ichthyosis" as your search term in the Rare Disease Database.)

Other forms of ichthyosis include Sjogren-Larsson syndrome, Netherton syndrome, Refsum syndrome, Darier disease, Conradi- Hunermann syndrome, Chanarin-Dorfman syndrome, and Epidermolytic hyperkeratosis. (Search under each name for more information on that disorder in the Rare Disease Database.)

Ichthyosis hystrix, Curth-Macklin type 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.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Ichthyosis Hystrix Curth-Macklin Type; IHCM. Entry Number; 146950: Last Edit Date; 3/11/2003.

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Ichthyosis Hystrix Gravior. Entry Number; 146600: Last Edit Date; 11/5/1994.

TEXTBOOKS
Sybert VA. Ichthyois. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:120-21.

Champion RH, Burton JL, Ebling FJG. Eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992:1340-41.

REVIEW ARTICLES
Ishida-Yamamoto A, Takahash H, Iizuka H. Lessons from disorders of epidermal differentiation-associated keratins. Histol Histopathol. 2002;17:331-38.

Anton-Lamprecht I. Ultrastructural identification of basic abnormalities as clues to genetic disorders of the epidermis. J Invest Dermatol. 1994;103(5 Suppl):6S-12S.

JOURNAL ARTICLE
Ishida-Yamamoto A. Richard G, Takahashi H, et al. In vivo studies of mutant keratin 1 in ichthyosis hystrix Curth-Macklin. J Invest Dermatol. 2003;120:498-500.

Bonifas JM, Bare JW, Chen MA, et al. Evidence against keratin gene mutations in a family with ichthyosis hystrix Curth-Macklin. J Invest Dermatol. 1993;101:890-91.

Niemi KM, Virtanen I, Kanerva L, et al. Altered keratin expression in ichthyosis hystrix Curth-Macklin. A light and electron microscopic study. Arch Dermatol Res. 1990;282:227-33.

Kanerva L, Karvonen J, Oikarinen A, et al. Ichthyosis hystrix (Curth-Macklin). Light and electron microscopic studies performed before and after etretinate treatment. Arch Dermatol. 1984;120:1218-23.