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Description
Harlequin ichthyosis is a severe genetic disorder that affects the skin. Infants with this condition are born prematurely 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 in babies with harlequin ichthyosis. Affected infants also have feeding problems.
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 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.
Following the newborn period, the hard, skin plates are shed and the skin develops widespread scales and redness.
It used to be very rare for affected infants to survive the newborn period. However, with intensive medical support and improved treatment, babies with this disorder now have a better chance of living into childhood and early adulthood.
Frequency
Harlequin ichthyosis is very rare; its exact incidence is unknown.
Causes
Variants (also known as 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) and enzymes in the outermost layer of skin (the epidermis).
Some variants in the ABCA12 gene prevent the cell from making any ABCA12 protein. Other variants 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 before and after birth, resulting in the severe skin abnormalities 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 variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Autosomal recessive congenital ichthyosis 4B
- Harlequin baby syndrome
- HI
- Ichthyosis congenita, harlequin fetus type
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Clinical Trials
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Hovnanian A. Harlequin ichthyosis unmasked: a defect of lipid transport. J Clin Invest. 2005 Jul;115(7):1708-10. doi: 10.1172/JCI25736. 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. doi: 10.1086/429844. Epub 2005 Mar 8. Citation on PubMed or Free article on PubMed Central
- Rajpopat S, Moss C, Mellerio J, Vahlquist A, Ganemo A, Hellstrom-Pigg M, Ilchyshyn A, Burrows N, Lestringant G, Taylor A, Kennedy C, Paige D, Harper J, Glover M, Fleckman P, Everman D, Fouani M, Kayserili H, Purvis D, Hobson E, Chu C, Mein C, Kelsell D, O'Toole E. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol. 2011 Jun;147(6):681-6. doi: 10.1001/archdermatol.2011.9. Epub 2011 Feb 21. Citation on PubMed
- Richard G. Autosomal Recessive Congenital Ichthyosis. 2001 Jan 10 [updated 2023 Apr 20]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. 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. doi: 10.1038/sj.jid.5700455. Epub 2006 Aug 10. Citation on PubMed
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