Harlequin type ichthyosis

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Harlequin type ichthyosis
ICD-10 Q80.4
ICD-9 757.1
OMIM 242500
DiseasesDB 30052
eMedicine derm/192 
MeSH D017490

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Harlequin-type ichthyosis (also harlequin ichthyosis, ichthyosis congenita, or keratosis diffusa fetalis), a skin disease, is the most severe form of congenital ichthyosis, characterized by a thickening of the keratin layer in fetal human skin. In sufferers of the disease, the skin contains massive, diamond-shaped scales, and tends to give off a reddish color. In addition, the eyes, ears, mouth, and other appendages may be abnormally contracted. The scaly keratin greatly limits the child's movement. Because the skin is cracked where normal skin would fold, it is easily pregnable by bacteria and other contaminants, resulting in serious risk of fatal infection.

Sufferers are known as harlequin fetuses, harlequin babies, or harlequins.

The harlequin-type designation comes from both the baby's apparent facial expression and the diamond-shape of the scales (resembling the costume of Arlecchino), which are caused by severe hyperkeratosis. The disease can be diagnosed in the uterus by way of fetal skin biopsy or by morphologic analysis of amniotic fluid cells obtained by amniocentesis. In addition, doctors can now usually recognize common features of the disease through ultrasound, and follow up with 3D ultrasound can diagnose the condition.

Features

The features of sufferers are deformed facially and cranially. The ears may be very poorly developed or absent entirely, as may the nose. The eyelids are severely everted (ectropion), which leaves the eyes and the area around them very susceptible to trauma. They often bleed upon birth. The lips, pulled by the dry skin, are fixed into a wide grimace (Eclabium). Arms, feet, and fingers are almost always deformed in such a way that they cannot bend properly, and may be below the normal size. They present Hypoplasia in the fingers, therefore, they cannot grab things properly, or they can barely touch them. Polydactyly, a condition in which one has more than the usual number of toes or fingers, has also been found in these infants.

They are extremely susceptible to changes in temperature due to their armor-like skin, which prevents normal heat loss. This can result in hyperthermia. Their respiration is also restricted by the skin, which impedes the chest wall from expanding and drawing in enough air. This can lead to hyperventilation and respiratory failure. Harlequins are often dehydrated, as their plated skin is not well suited to keeping water in.

Treatment and prognosis

In the past, the disorder was invariably fatal, whether due to dehydration, infection (sepsis), restricted respiration due to the plating, or other related causes. The most common cause of death was systemic infection and sufferers rarely survived for more than a few days. However there have been improvements in care, most notably the drug Isotrex. Some patients have survived into adolescence and, in very rare cases, lived to adulthood.

Genetics

Mutations in the ABCA12 gene cause harlequin ichthyosis.[1][2] The ABCA12 gene makes a protein that is essential for the normal development of skin cells. Although the protein's exact function is unknown, researchers believe that it probably plays a major role in the transport of lipids (fats) in the outermost layer of skin (the epidermis). Mutations in the ABCA12 gene lead to the production of an abnormally small version of the protein that cannot transport lipids properly. The loss of functional ABCA12 protein disrupts the normal development of the epidermis, preventing the skin from forming an effective barrier and resulting in the hard, thick scales characteristic of harlequin ichthyosis.

This condition is likely inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

History

The disease has been known since around 1750, and was first described in the diary of Rev. Oliver Hart:[3]

"On Thursday, April þe 5, 1750, I went to see a most deplorable object of a child, born the night before of one Mary Evans in 'Chas'town. It was surprising to all who beheld it, and I scarcely know how to describe it. The skin was dry and hard and seemed to be cracked in many places, somewhat resembling the scales of a fish. The mouth was large and round and open. It had no external nose, but two holes where the nose should have been. The eyes appeared to be lumps of coagulated blood, turned out, about the bigness of a plum, ghastly to behold. It had no external ears, but holes where the ears should be. The hands and feet appeared to be swollen, were cramped up and felt quite hard. The back part of the head was much open. It made a strange kind of noise, very low, which I cannot describe. It lived about forty-eight hours and was alive when I saw it."

Over a hundred cases have been reported worldwide in modern times. Neither gender nor ethnicity seem to affect the likelihood of a child having the disorder. A disproportionately high number of children have consanguineous parents. Those from families with a history of severe skin disorders may have a higher risk of birthing a harlequin child.

References

  1. "BBC NEWS". Retrieved 2007-07-03. 
  2. Kelsell DP, Norgett EE, Unsworth H; et al. (2005). "Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis". Am. J. Hum. Genet. 76 (5): 794–803. PMID 15756637. doi:10.1086/429844. 
  3. Hovnanian A (2005). "Harlequin ichthyosis unmasked: a defect of lipid transport". J. Clin. Invest. 115 (7): 1708–10. PMID 16007249. doi:10.1172/JCI25736. 

Additional Resources

  • Akiyama M (1999). "The pathogenesis of severe congenital ichthyosis of the neonate". J. Dermatol. Sci. 21 (2): 96–104. PMID 10511478. 
  • Moskowitz DG, Fowler AJ, Heyman MB; et al. (2004). "Pathophysiologic basis for growth failure in children with ichthyosis: an evaluation of cutaneous ultrastructure, epidermal permeability barrier function, and energy expenditure". J. Pediatr. 145 (1): 82–92. PMID 15238912. doi:10.1016/j.jpeds.2004.03.052. 

External links

Note: The links below contain media which graphically depict the effects of Harlequin type Ichthyosis on young infants.



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