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Ichthyosis, Harlequin Type

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NORD is very grateful to the members of the Medical and Scientific Advisory Board of the Foundation for Ichthyosis & Related Skin Types for assistance in the preparation of this report.

Synonyms of Ichthyosis, Harlequin Type

Disorder Subdivisions

General Discussion

Harlequin ichthyosis is a rare genetic skin disorder. The newborn infant is covered with plates of thick skin that crack and split apart. The thick plates can pull at and distort facial features and can restrict breathing and eating. Harlequin infants need to be cared for in the neonatal intensive care unit immediately. Harlequin ichthyosis is inherited as an autosomal recessive trait.


Infants born with Harlequin ichthyosis are covered in thick plate-like scales of skin. The tightness of the skin pulls around the eyes and the mouth, forcing the eyelids and lips to turn inside out, revealing the red inner linings. The chest and abdomen of the infant may be severely restricted by the tightness of the skin, making breathing and eating difficult. The hands and feet may be small and swollen, and partially flexed. The ears may appear to be misshapen or missing, but are really fused to the head by the thick skin.

Premature birth is typical, leaving the infants at risk for complications from early delivery. These infants are also at high risk for difficulty breathing, infection, low body temperature, dehydration, and hypernatremia (elevated levels of sodium in the blood). Constriction and swelling of the mouth may interfere with the suck response and infants may need tube feeding. The baby's corneas need to be lubricated and protected if the eyelids are forced open by the tightness of the skin.


Harlequin type ichthyosis is a hereditary disorder transmitted through autosomal recessive genes. In recessive disorders, the condition appears when the person inherits the same defective gene for the same trait from each parent. If the individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but will not show the condition. The risk of transmitting the disease to the children of a couple, both of whom are carriers for the recessive disorder, is approximately 25 percent per pregnancy.

Investigators have determined that Harlequin type ichthyosis is caused by disruptions or changes (mutations) to the ABCA12 gene located on chromosome 2 (2q34). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22 and an additional 23rd pair of sex chromosomes, which include one X and one Y chromosome in males and two X chromosomes in females. 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 2q34" refers to band 34 on the long arm of chromosome 2. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Affected Populations

Harlequin type ichthyosis is a rare skin disorder that affects infants before birth. Males and females are affected in equal numbers. It affects approximately one in 500,000 persons. Harlequin type ichthyosis occurs in about seven births annually in the United States.

Related Disorders

Symptoms of the following disorders may be similar to Harlequin type ichthyosis.

Ichthyosis congenita (collodion baby; congenital ichthyosiform erythroderma; xeroderma; desquamation of the newborn) is an inherited skin disorder. It is characterized by generalized, abnormally red, dry, and rough skin with large coarse and fine white scales. Itchiness (pruritus) usually also develops. Skin on the palms of the hands and soles of the feet can be abnormally thick. (For more information, choose "Ichthyosis Congenital" as your search term in the Rare Disease Database.)

Lamellar ichthyosis is an inherited skin disorder characterized by broad, dark, plate-like scales separated by deep cracks. Lamellar ichthyosis may also cause reddened skin (erythroderma), thickened skin on the palms and soles and decreased sweating with heat intolerance. (For more information on lamellar ichthyosis, choose "Ichthyosis, Lamellar"as your search term in the Rare Disease Database.)

Standard Therapies

The thick, plate-like skin of Harlequin type ichthyosis will gradually split and peel off over several weeks. Antibiotic treatment may be necessary to prevent infection at this time. Administration of oral etretinate (1mg./kg. body weight) may accelerate shedding of the thick scales. Most Harlequin infants will need one-on-one nursing care for the first several weeks of life.

After the thick plates peel off, the skin is left dry and reddened, and may be covered in large thin scales. The skin symptoms are treated by applying skin softening emollients. This can be particularly effective after bathing while the skin is still moist. Skin barrier repair formulas containing ceramides or cholesterol, moisturizers with petrolatum or lanolin, and mild keratolytics (products containing alpha-hydroxy acids or urea) can all work to keep the skin moisturized and pliable, and prevent cracking and fissuring that can lead to infection.

Severe cases of ichthyosis can be treated systemically with oral retinoids. Retinoids are used only in severe cases of ichthyosis due to their known toxicity and other complications.

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:

Ichthyosis, Harlequin Type Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:


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Kelsell DP, Norgett EE, Unsworth H, et al., Mutations in ABCA12 underlie severe congenital harlequin ichthyosis. Am J Hum Genet. 2005;76:794-803.

Elias, PM, Williams, ML. Enlightened Therapy of the Disorders of Cornification. Clinics in Dermatology. 2003; 21: 269 - 273.

Thomas, C. Harlequin Ichthyosis, Treating a Rare Hereditary Disorder. Advance for Physician Assistants. December 2000: 32 - 48.

Saunders, B, Freedman, C, Nyhan, WL, Rice-Asaro, M, and Mannino, F. Influence of nutrition on growth and development of a long-surviving Harlequin fetus. Dysmorphology and Clinical Genetics. 1992;6:2-8.

Buxman, M, et al. Therapeutic activity of lactate 12% lotion in the treatment of ichthyosis. Active versus vehicle and active versus a petroleum cream. J Am Acad Dermatol. December 1986; 15(6): 1253-1258.

Williams, ML, et al. Genetically Transmitted, Generalized Disorders of Cornification. The Ichthyoses. Dermatol Clin. January 1987; 5(1): 155-78.

Lawlor, F and Pheris, S. Harlequin fetus successfully treated with etretinate. Brit J Derm. 1985;112:585-90.

Report last updated: 2008/04/05 00:00:00 GMT+0