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Genetics Home Reference: your guide to understanding genetic conditions
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Harlequin ichthyosis

Reviewed November 2008

What is harlequin ichthyosis?

Harlequin ichthyosis is a severe genetic disorder that mainly affects the skin. Infants with this condition are born with very hard, thick skin covering most of their bodies. The skin forms large, diamond-shaped plates that are separated by deep cracks (fissures). These skin abnormalities affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties and respiratory failure.

The skin normally forms a protective barrier between the body and its surrounding environment. The skin abnormalities associated with harlequin ichthyosis disrupt this barrier, making it more difficult for affected infants to control water loss, regulate their body temperature, and fight infections. Infants with harlequin ichthyosis often experience an excessive loss of fluids (dehydration) and develop life-threatening infections in the first few weeks of life. It used to be very rare for affected infants to survive the newborn period. However, with intensive medical support and improved treatment, people with this disorder now have a better chance of living into childhood and adolescence.

How common is harlequin ichthyosis?

Harlequin ichthyosis is very rare; its exact incidence is unknown.

What genes are related to harlequin ichthyosis?

Mutations in the ABCA12 gene cause harlequin ichthyosis. The ABCA12 gene provides instructions for making a protein that is essential for the normal development of skin cells. This protein plays a major role in the transport of fats (lipids) in the outermost layer of skin (the epidermis). Some mutations in the ABCA12 gene prevent the cell from making any ABCA12 protein. Other mutations lead to the production of an abnormally small version of the protein that cannot transport lipids properly. A loss of functional ABCA12 protein disrupts the normal development of the epidermis, resulting in the hard, thick scales characteristic of harlequin ichthyosis.

Related Gene(s)

Changes in this gene are associated with harlequin ichthyosis.

  • ABCA12

How do people inherit harlequin ichthyosis?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of harlequin ichthyosis?

These resources address the diagnosis or management of harlequin ichthyosis and may include treatment providers.

  • Gene Review: Autosomal Recessive Congenital Ichthyosis (http://www.ncbi.nlm.nih.gov/books/NBK1420)
  • Genetic Testing Registry: Autosomal recessive congenital ichthyosis 4B (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0239849)

You might also find information on the diagnosis or management of harlequin ichthyosis in Educational resources (http://www.ghr.nlm.nih.gov/condition/harlequin-ichthyosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/harlequin-ichthyosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about harlequin ichthyosis?

You may find the following resources about harlequin ichthyosis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for harlequin ichthyosis?

  • Harlequin baby syndrome
  • HI
  • Ichthyosis Congenita, Harlequin Fetus Type

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about harlequin ichthyosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding harlequin ichthyosis?

autosomal ; autosomal recessive ; cell ; dehydration ; epidermis ; fetus ; gene ; ichthyosis ; incidence ; inherited ; protein ; recessive ; respiratory ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Akiyama M, Sakai K, Sugiyama-Nakagiri Y, Yamanaka Y, McMillan JR, Sawamura D, Niizeki H, Miyagawa S, Shimizu H. Compound heterozygous mutations including a de novo missense mutation in ABCA12 led to a case of harlequin ichthyosis with moderate clinical severity. J Invest Dermatol. 2006 Jul;126(7):1518-23. Epub 2006 May 4. (http://www.ncbi.nlm.nih.gov/pubmed/16675967?dopt=Abstract)
  • Akiyama M, Sugiyama-Nakagiri Y, Sakai K, McMillan JR, Goto M, Arita K, Tsuji-Abe Y, Tabata N, Matsuoka K, Sasaki R, Sawamura D, Shimizu H. Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. J Clin Invest. 2005 Jul;115(7):1777-84. (http://www.ncbi.nlm.nih.gov/pubmed/16007253?dopt=Abstract)
  • Akiyama M. The pathogenesis of severe congenital ichthyosis of the neonate. J Dermatol Sci. 1999 Sep;21(2):96-104. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10511478?dopt=Abstract)
  • Gene Review: Autosomal Recessive Congenital Ichthyosis (http://www.ncbi.nlm.nih.gov/books/NBK1420)
  • Hovnanian A. Harlequin ichthyosis unmasked: a defect of lipid transport. J Clin Invest. 2005 Jul;115(7):1708-10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16007249?dopt=Abstract)
  • Kelsell DP, Norgett EE, Unsworth H, Teh MT, Cullup T, Mein CA, Dopping-Hepenstal PJ, Dale BA, Tadini G, Fleckman P, Stephens KG, Sybert VP, Mallory SB, North BV, Witt DR, Sprecher E, Taylor AE, Ilchyshyn A, Kennedy CT, Goodyear H, Moss C, Paige D, Harper JI, Young BD, Leigh IM, Eady RA, O'Toole EA. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet. 2005 May;76(5):794-803. Epub 2005 Mar 8. (http://www.ncbi.nlm.nih.gov/pubmed/15756637?dopt=Abstract)
  • Moskowitz DG, Fowler AJ, Heyman MB, Cohen SP, Crumrine D, Elias PM, Williams ML. Pathophysiologic basis for growth failure in children with ichthyosis: an evaluation of cutaneous ultrastructure, epidermal permeability barrier function, and energy expenditure. J Pediatr. 2004 Jul;145(1):82-92. (http://www.ncbi.nlm.nih.gov/pubmed/15238912?dopt=Abstract)
  • Thomas AC, Cullup T, Norgett EE, Hill T, Barton S, Dale BA, Sprecher E, Sheridan E, Taylor AE, Wilroy RS, DeLozier C, Burrows N, Goodyear H, Fleckman P, Stephens KG, Mehta L, Watson RM, Graham R, Wolf R, Slavotinek A, Martin M, Bourn D, Mein CA, O'Toole EA, Kelsell DP. ABCA12 is the major harlequin ichthyosis gene. J Invest Dermatol. 2006 Nov;126(11):2408-13. Epub 2006 Aug 10. (http://www.ncbi.nlm.nih.gov/pubmed/16902423?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2008
Published: December 16, 2014