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Harlequin ichthyosis

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Description

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.

Frequency

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

Causes

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.

Inheritance

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.

Other Names for This Condition

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

Additional Information & Resources

Genetic and Rare Diseases Information Center

Research Studies from ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

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. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central
  • Akiyama M. The pathogenesis of severe congenital ichthyosis of the neonate. J Dermatol Sci. 1999 Sep;21(2):96-104. Review. Citation on PubMed
  • Hovnanian A. Harlequin ichthyosis unmasked: a defect of lipid transport. J Clin Invest. 2005 Jul;115(7):1708-10. Review. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed
  • Richard G. Autosomal Recessive Congenital Ichthyosis. 2001 Jan 10 [updated 2017 May 18]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1420/ Citation on PubMed
  • 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. Citation on PubMed
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