Last updated:
July 16, 2019
Years published: 1988, 1989, 1991, 1992, 1993, 1997, 2004, 2006, 2019
NORD gratefully acknowledges François Lagacé, MD Candidate, McGill University School of Medicine, and Edel O’Toole, MB, PhD, FRCP, Professor of Molecular Dermatology, Centre Lead, Queen Mary University of London, for assistance in the preparation of this report.
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 in an autosomal recessive pattern.
Infants 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. Infants born with harlequin ichthyosis may also have a flat nose (depressed nasal bridge), abnormal hearing, frequent respiratory infections, and decreased joint mobility.
Premature birth is typical, leaving the infants at risk for complications from early delivery. These infants are also at high risk for 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 ichthyosis is caused by changes (mutations) in the ABCA12 gene, which gives instructions for making a protein that is necessary for skin cells to develop normally. It plays a key role in the transport of fats (lipids) to most superficial layer of the skin (epidermis), creating an effective skin barrier. When this gene is mutated, the skin barrier is disrupted.
Harlequin ichthyosis is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal 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 abnormal 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 is 25%. The risk is the same for males and females.
Harlequin ichthyosis affects males and females in equal numbers. This condition affects approximately one in 500,000 persons or about seven births annually in the United States.
Harlequin ichthyosis is diagnosed at birth based on the child’s physical appearance. Prenatal testing may be possible by testing fetal DNA for mutations in the ABCA12 gene. In addition, some of the features of harlequin ichthyosis maybe seen on ultrasound during the second trimester and onward.
A multi-disciplinary team is involved in the care of infants with harlequin ichthyosis as soon as they are born. This has been shown to improve outcomes and reduce complications such as respiratory distress, dehydration, electrolyte imbalances, impaired thermoregulation, systemic bacterial infections, and feeding difficulties. Early treatment with oral retinoids is also thought to improve outcomes. However, they are only used in severe cases due to their known toxicity and side effects.
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 acitretin 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. Many patients with severe ichthyosis exfoliate manually by rubbing off the thick scale with special exfoliating gloves with a rough surface. 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. Removal of damaged tissue (debridement) from the fingers may be needed if they are constricted by bands of skin to avoid a loss of circulation.
Information on current clinical trials is posted on the Internet at https://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:
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Some current clinical trials also are posted on the following page on the NORD website:
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For information about clinical trials sponsored by private sources, contact:
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For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Akiyama M, Sugiyama-Nakagiri Y, Sakai K, et al., Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. J Clin Invest. 2005;115:1777-84.
Uitto J. The gene family of ABC transporters novel mutations, new phenotypes. Trends Mol Med. 2005;11:341-3.
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.
Ahmed H, O’Toole EA. Recent advances in the genetics and management of harlequin ichthyosis. Pediatric dermatology. 2014;31(5):539-46.
Sugiura K, Akiyama M. Update on autosomal recessive congenital ichthyosis: mRNA analysis using hair samples is a powerful tool for genetic diagnosis. Journal of Dermatological Science. 2015;79(1):4-9.
Shibata A, Ogawa Y, Sugiura K, Muro Y, Abe R, Suzuki T, et al. High survival rate of harlequin ichthyosis in Japan. Journal of the American Academy of Dermatology. 2014;70(2):387-8.
INTERNET
Harlequin ichthyosis. Genetics Home Reference. Review Date: November 2008. 6pp. https://ghr.nlm.nih.gov/condition/harlequin-ichthyosis#genes Accessed May 1, 2019
Harlequin Ichthyosis. Genetic and Rare Diseases Information Center. Last updated: 2/6/2015. https://rarediseases.info.nih.gov/diseases/6568/harlequin-ichthyosis Accessed May 1, 2019.
Choate K. Overview and Classification of the Inherited Ichthyoses. UpToDate. topic last updated: Mar 05, 2019. https://www.uptodate.com/contents/overview-and-classification-of-the-inherited-ichthyoses. Accessed May 1, 2019.
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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