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Ichthyosis, Chanarin Dorfman Syndrome

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Synonyms of Ichthyosis, Chanarin Dorfman Syndrome

Disorder Subdivisions

General Discussion

Chanarin Dorfman syndrome is a rare hereditary disorder of fat (lipid) metabolism. It is characterized by scaly skin (ichthyosis), degeneration of the muscles (myopathy), and abnormal white blood cells with small spaces (vacuoles) filled with fat (lipids).

Symptoms

Chanarin Dorfman syndrome is characterized by moderately red, itchy, dry skin and other skin changes (eczematous dermatitis). Prominent fat (lipid) droplets appear in most circulating white blood cells. Lipid droplets are also present in numerous other cells, including those of the skin and the ducts of sweat glands.

Degeneration of the muscles may be identified through neurologic testing, and muscle enzyme levels in the blood are elevated. The liver biopsy samples of all patients have shown severe fatty change, but this may not be reflected in liver function studies. Both nerve deafness and cataracts are present in some patients with Chanarin Dorfman syndrome. Abnormally slow development and growth may also be symptoms of this disorder.

Causes

Chanarin-Dorfman syndrome is the result of an inborn error of metabolism and is transmitted as an autosomal recessive trait. It is associated with a gene on the short arm of chromosome 3 (3p21).

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 3p21" refers to band 21 on the short arm of chromosome 3. 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.

Affected Populations

Chanarin Dorfman Syndrome is a very rare disorder which tends to affect persons of Middle Eastern or Mediterranean descent. It affects males and females in equal numbers.

Related Disorders

Symptoms of the following disorders can be similar to those of Chanarin Dorfman Syndrome. Comparisons may 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 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. (For more information, choose "Ichthyosis" as your search term in the Rare Disease Database.)

CHILD Syndrome (Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects; Ichthyosiform Erythroderma, Unilateral, with Ipsilateral Malformations, especially Absence Deformity of Limbs) is a rare, hereditary disorder characterized by scaly red skin (ichthyosis) and deformities of the limbs on one side of the body. It occurs much more frequently in males than in females.

Ichthyosis Congenita (Collodion Baby; Congenital Ichthyosiform Erythroderma; Desquamation of Newborn) is an inherited skin disorder. It is characterized by generalized, abnormally red (erythroderma), dry and rough skin with large, coarse scales. Itchiness 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, and Epidermolytic Hyperkeratosis. (Choose the appropriate name as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
Diagnosis of Chanarin Dorfman syndrome can be made when blood taken from a finger, toe, heel, or ear shows fat droplets in certain white blood cells.

Treatment
Dermatologic symptoms are 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 can be effective against skin symptoms of Chanarin Dorfman syndrome, but can cause toxic effects on the bones in some cases, especially if taken by pregnant women. 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.

Treatment of other features of Chanarin Dorfman syndrome is symptomatic and supportive.

Investigational Therapies

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

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

Organizations related to Ichthyosis, Chanarin Dorfman Syndrome

References

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.

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

JOURNAL ARTICLES
Lefevre C, Jobard F, Caux F, et al. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. Am J Hum Genet. 2001;69:1002-12.

Fischer J, Faure A, Bouadjar B, et al. Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity. Am J Hum Genet. 2000;66:904-13.

Wessalowski R, Schroten H, Neuen-Jacob E, et al. Multisystem triglyceride storage disorder without ichthyosis in two siblings. Acta Paediatr. 1994;83:93-98.

Williams ML, Coleman RA, Placezk D, et al. Neutral lipid storage disease: a possible functional defect in phospholipid-linked triacylglycerol metab-olism. Biochim Biophys Acta. 1991;1096:162-69.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Triglyceride Storage Disease with Impaired Long-Chain Fatty acid Oxidation. Entry Number; 275630: Last Edit Date; 8/27/2003.

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Comparative Gene Identification 58. Entry Number; 604780: Last Edit Date; 1/14/2002.

Neutral Lipid Storage Disease. About Ichthyosis. Foundation for Ichthyosis and Related Skin Types (F.I.R.S.T.) nd. 2pp.
www.scalyskin.org/content.cfm?ContentID=102&ColumnID=14

Chanarin-Dorfman disease Information. i-medicine. Last update 2003-10-02.
www.diseasedatabase.com/sieve/item1.asp?glngUserChoice=32708

Report last updated: 2008/04/14 00:00:00 GMT+0