written by: bjlbyron•edited by: lrohner•updated: 11/10/2010
Harlequin ichthyosis is an inherited skin disorder that is often lethal and always very debilitating. Read on to learn more about this rare genetic condition and its underlying genetic cause.
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What Is Harlequin Ichthyosis?
Harlequin ichthyosis (HI) is an autosomal recessive genetic disorder in which sufferers experience a number of skin problems. Those who have HI typically are born with thick and tough skin (i.e., their skin becomes dense and "armor"-like) which covers all or a large portion of their bodies. The skin of these affected individuals often features yellow plates of scales and has deep red fissures. Other symptoms commonly seen in HI sufferers include skin defects that affect the shape of various body parts, such as the ears, nose, mouth and eyelids. These defects can cause the skin of the face to appear tight, pulled back and "frog-like".
Other commonly experienced HI symptoms include:
Chest tightness, which can cause great breathing difficulty and even respiratory failure
Increased water loss through the skin (which can lead to severe dehydration)
Decreased ability of the body to regulate body temperature
It was common for virtually every infant who was born with HI to die soon after birth, typically due to infection. Recent medical advances, however, have enabled some individuals who are inflicted with HI to survive for several years. Fortunately, HI is an extremely rare disorder, which only appears once in every several thousand births.
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What Is Known About The Genetics Of Harlequin Ichthyosis?
Although HI is inherited in an autosomal recessive fashion, it has been only in recent years that human molecular geneticists discovered the underlying cause of HI. Specifically, these scientists determined that mutations in a gene that is designated ABCA12 are responsible for causing HI.
In normal individuals, the ABCA12 gene encodes a protein, a type of ATP-binding cassette reporter protein, that is necessary for the normal development of skins cells. A function of ATP-binding cassette reporter proteins is to transport various molecules that are needed in the skin across cell membranes. One class of molecules that these proteins transport is lipids (fats), which are essential components of the outer layer of the skin (which is known specifically as the epidermis). Those who are mutant in both of their copies of the ABCA12 gene are unable to synthesize fully functional ABCA12 version of the ATP-binding cassette reporter protein (or may not make this protein at all). Due to this deficiency, lipids are not sufficiently carried from deep within the skin to its outer epidermal layer, which causes these individuals to suffer one or more of the skin problems that were described in the previous section.
This article is only meant to provide some basic information regarding the genetic condition known as harlequin ichthyosis. If you have any further questions regarding this inherited disorder, please contact your doctor or consult a genetic counselor.
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A. Hovnanian, Harlequin ichthyosis unmasked: a defect of lipid transport, The Journal Of Clinical Investigation 115:1708-1710 (2005). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1159155/
Genetics Home Reference, National Institutes of Health, ABCA12: http://ghr.nlm.nih.gov/gene/ABCA12
Genetics Home Reference, National Institutes of Health, Harlequin ichthyosis: http://ghr.nlm.nih.gov/condition/harlequin-ichthyosis
M. Akiyama et al., Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer, The Journal Of Clinical Investigation 115:1777-1784 (2005). http://www.jci.org/articles/view/24834