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

• Ichthyosis Vulgaris
• X-linked Ichthyosis
• Epidermolytical Hyperkeratosis

Lamellar ichthyosis is characterized by generalized abnormal red, dry and rough skin. Large, coarse scales also occur on the skin, causing itchiness. These characteristics appear over most of the body. Skin on the palms of the hands and soles of the feet is abnormally thick.

If the top layers of the skin (stratum corneum) of the scalp become very thick, the follicles of the hair, and the hair itself, may become encased and fall out (scarring alopecia). Similarly, if the thickening of the skin interferes with the functions of the sweat glands, heat intolerance may develop and overheating could become a threat.

LI is an autosomal recessive inherited disorder. The gene at fault codes for an enzyme (transglutaminase 1) that is essential for the development of a structurally stable layer of skin. The enzyme works by creating strong and stable "cross-links" between the several proteins involved in the process. The gene associated with LI has been tracked to a location on the long arm of chromosome 14 (14q11.2).

Because a few patients have been found to have a form of Lamellar ichthyosis with normal enzyme activity, researchers have identified the following even rarer forms of the disorder and the locations of associated genes: LI-2 (2q33-q35); LI-3 (19p12-q12); LI-4 (unknown); and LI-5 (17p13.2-p13.1).

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 11p13" refers to band 13 on the short arm of chromosome 11. 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.

Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

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.

LI-1 affects males and females equally and has a prevalence in the USA of about 1 per 200,000 newborns. Ethnicity does not appear to play a role in the incidence or prevalence of the disorder.

Symptoms of the following disorders may be similar to those of lamellar ichthyosis:

Ichthyosis vulgaris is an autosomal dominant inherited disorder with onset in childhood. 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.

X-linked ichthyosis is an inherited disorder that occurs only in males, with onset at birth or during infancy. 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.) It is characterized by large, dark, sometimes fine scales which are prominent on the neck and trunk. Skin on the palms and soles of the feet is normal. Opacities in the cornea of the eye occur in this form of Ichthyosis.

Epidermolytical hyperkeratosis or bullous congenital ichthyosiform erythroderma is an autosomal dominant inherited disorder with onset at birth. It is characterized by thick warty scales on most of the body, especially in the creases of bent (flexural) skin surfaces. Blisters may also occur.

Diagnosis
In most instances the appearance of the skin determines the diagnosis but a family history and physical examination are often required to rule out other possible causes of scaly, dry skin.

Some physicians may examine skin tissue under a light microscope or even under an electron microscope.

Treatment
The dry scaly skin of lamellar 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.

Drugs derived from Vitamin A (retinoids) such as tretinoin, motretinide, and etretinate are often effective against symptoms of 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, and should be avoided by women of child-bearing age.

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 website.

For information about clinical trials being conducted at the National Institutes of Health (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

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Ichthyosis, Lamellar, 1; LI1. Entry Number: 242300, Last Edit Date: 3/18/2003; Ichthyosis, Lamellar, 2; LI2. Entry Number: 601277, Last Edit Date: 7/25/2003; Ichthyosis, Lamellar, 3; LI3. Entry Number: 604777, Last Edit Date: 5/22/2000; Ichthyosis, Lamellar, Autosomal Dominant Form. Entry Number: 146750, Last Edit Date: 11/5/1994; Ichthyosis, Lamellar, 5. Entry Number: 606545, Last Edit Date: 7/25/2003.

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

Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:831-32.

Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:1192.

Champion RH, Burton JL, Ebling FJG. eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992:1329-65.

REVIEW ARTICLES
Akiyama M, Sawamura D, Shimizu H. The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis. Clin Exp Dermatol. 2003;28:235-40.

DiGiovanna JJ, Robinson-Bostom L. Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol. 2003;4:81-95.

Spirito F, Meneguzzi G, Danos O, et al. Cutaneous gene transfer and therapy: the present and the future. J Gene Med. 2001;3:21-31

McGrath JA, Eady RA. Recent advances in the molecular basis of inherited skin diseases. Adv Genet. 2001;43:1-32.

FROM THE INTERNET
Ichthyosis, Lamellar. emedicine. Last Updated: 2/13/2003. 10pp.
www.emedicine.com/derm/topic190.htm

Lehrer M. Ichthyosis vulgaris. MEDLINEplus. Medical Encyclopedia. Update date: 12/1/2001. 3pp.
www.nlm.nih.gov/medlineplus/ency/article/001451.htm

Ichthyosis. British Association of Dermatologists. nd. 5pp.
www.bad.org.uk/patients/skin_disease_info/ichthyosis/

Zambon F. RECESSIVE LAMELLAR ICHTHYOSIS. University of Padua. nd. 6pp.
http://malattierare.pediatria.unipd.it/pubblicaMR/mr_dx_ing.asp?mr=475