NORD gratefully acknowledges the members of the Medical and Scientific Advisory Board of the Foundation for Ichthyosis & Related Skin Types for assistance in the preparation of this report.
Harlequin ichthyosis is a rare genetic skin disorder. The newborn infant is covered with plates of thick skin that crack and split apart. The thick plates can pull at and distort facial features and can restrict breathing and eating. Harlequin infants need to be cared for in the neonatal intensive care unit immediately. Harlequin ichthyosis is inherited as an autosomal recessive trait.
Infants born with Harlequin ichthyosis are covered in thick plate-like scales of skin. The tightness of the skin pulls around the eyes and the mouth, forcing the eyelids and lips to turn inside out, revealing the red inner linings. The chest and abdomen of the infant may be severely restricted by the tightness of the skin, making breathing and eating difficult. The hands and feet may be small and swollen, and partially flexed. The ears may appear to be misshapen or missing, but are really fused to the head by the thick skin.
Premature birth is typical, leaving the infants at risk for complications from early delivery. These infants are also at high risk for difficulty breathing, infection, low body temperature, dehydration, and hypernatremia (elevated levels of sodium in the blood). Constriction and swelling of the mouth may interfere with the suck response and infants may need tube feeding. The baby’s corneas need to be lubricated and protected if the eyelids are forced open by the tightness of the skin.
Harlequin type ichthyosis is a hereditary disorder transmitted through autosomal recessive genes. In recessive disorders, the condition appears when the person inherits the same defective gene for the same trait from each parent. If the individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but will not show the condition. The risk of transmitting the disease to the children of a couple, both of whom are carriers for the recessive disorder, is approximately 25 percent per pregnancy.
Investigators have determined that Harlequin type ichthyosis is caused by disruptions or changes (mutations) to the ABCA12 gene located on chromosome 2 (2q34). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22 and an additional 23rd pair of sex chromosomes, which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 2q34” refers to band 34 on the long arm of chromosome 2. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Harlequin type ichthyosis is a rare skin disorder that affects infants before birth. Males and females are affected in equal numbers. It affects approximately one in 500,000 persons. Harlequin type ichthyosis occurs in about seven births annually in the United States.
The thick, plate-like skin of Harlequin type ichthyosis will gradually split and peel off over several weeks. Antibiotic treatment may be necessary to prevent infection at this time. Administration of oral etretinate (1mg./kg. body weight) may accelerate shedding of the thick scales. Most Harlequin infants will need one-on-one nursing care for the first several weeks of life.
After the thick plates peel off, the skin is left dry and reddened, and may be covered in large thin scales. The skin symptoms are treated by applying skin softening emollients. This can be particularly effective after bathing while the skin is still moist. Skin barrier repair formulas containing ceramides or cholesterol, moisturizers with petrolatum or lanolin, and mild keratolytics (products containing alpha-hydroxy acids or urea) can all work to keep the skin moisturized and pliable, and prevent cracking and fissuring that can lead to infection.
Severe cases of ichthyosis can be treated systemically with oral retinoids. Retinoids are used only in severe cases of ichthyosis due to their known toxicity and other complications.
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