Harlequin-type ichthyosis

Not to be confused with Harlequin syndrome.

Harlequin type ichthyosis
Classification and external resources
Harlequin fetus (1886)
ICD-10	Q80.4
ICD-9	757.1
OMIM	242500
DiseasesDB	30052
eMedicine	derm/192
MeSH	D017490

Harlequin-type ichthyosis (also known as "Harlequin baby", Harlequin ichthyosis, ichthyosis congenita, Ichthyosis fetalis, keratosis diffusa fetalis, "Harlequin fetus", and "Ichthyosis congenita gravior"), 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 have a reddish color. In addition, the eyes, ears, penis, and the appendages may be abnormally contracted. The scaly keratin greatly limits the child's movement. Because of resultant cracked skin in locations where normal skin would fold, it is easily pregnable by bacteria and other contaminants, resulting in serious risk of fatal infection.

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 to diagnose the condition.

It is associated with a mutation in the gene for the protein ABCA12.

Signs and symptoms

The features of the sufferers are severe cranial and facial deformities. 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 infection. 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 cracked 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 hypoventilation 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 always fatal, whether due to dehydration, infection (sepsis), restricted breathing 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 Isotretinoin (Isotrex). The oldest known survivor is 26-year old Nusrit "Nelly" Shaheen, who is in good health. Lifespan limitations have not yet been determined with the new treatments.

History

The disease has been known since 1750, and was first described in the diary of a cleric from Charleston, South Carolina, the Rev. Oliver Hart:

"On Thursday, April the 5th, 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."

Notable cases

• Nusrit "Nelly" Shaheen (born 1984) is the oldest known survivor with the condition. She lives in the UK and is one of nine children, four of whom also suffered from the condition and died as young children. Nelly lives an active lifestyle and is studying sports coaching and leadership at Hereward College.

• Hunter Steinitz (born 1994) is one of only twelve Americans suffering from the disease and is profiled on the National Geographic "Extraordinary Humans: Skin" special.

• Ryan Gonzalez (born 1986) is the oldest person in the United States living with the disease. He was featured in an episode of Medical Incredible.

References

• Akiyama M (1999). "The pathogenesis of severe congenital ichthyosis of the neonate". J Dermatol Sci. 21 (2): 96–104. doi:10.1016/S0923-1811(99)00024-9. 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. doi:10.1016/j.jpeds.2004.03.052. PMID 15238912. 

External links

• A Case Of Harlequin Fetus With Psoriasis In His Family. Article from the Internet Journal of Pediatrics and Neonatology.
• Medical Article from FIRST Foundation
• Profile of 15 year old surviving Harlequin
• Hospital photos and diagrams
• Information from the U.S. National Institutes of Health
• Genetic information