Harlequin Fetus Health Article

Definition

The term harlequin fetus is used to describe an extremely severe form of skin disease in which affected infants have thick, plate-like scales all over their bodies. This abnormality is present from birth. It leads to disfiguration of the facial features and limited movement of the arms, legs, fingers, and toes. Most affected infants die during the first several weeks of life, although longer-term survivors have been reported.

Description

Harlequin fetus represents the most severe presentation of inherited ichthyosis. The word ichthyosis, which is derived from the Greek word for fish, is a descriptive term used for a group of inherited disorders in which the skin is markedly thickened, ridged, and cracked. The term "harlequin ichthyosis" is therefore used interchangeably with "harlequin fetus." Other synonyms over time have included fetal ichthyosis, ichthyosis intrauterina, keratosis diffusa fetalis, congenital diffuse maligna keratoma, and malignant keratosis.

The ichthyoses as a group are due to a variety of underlying metabolic abnormalities. However, the net effect of each abnormality is the same: keratinization, or differentiation of the cells which make up the skin, does not occur normally. The ichthyoses are separated based on their clinical features and the age at which symptoms appear.

Ichthyosis of the newborn refers to those disorders that present either at birth or shortly thereafter. Each newborn ichthyosis may be due to a different genetic abnormality, even when there is some similarity between clinical features. The harlequin fetus, however, is such a distinct and striking disorder that it is rarely confused with other types of ichthyosis. Affected infants have thick, armor-like skin with deep cracks running in different directions all over their bodies. This gives the appearance of diamond-shaped plaques. The word "harlequin" is often used to describe a variegated pattern, or a combination of patches on a solid background of a contrasting color. The severe skin abnormality leads to an open, fish-mouth appearance as well as a turning outward of the eyelids. Abnormalities of the internal organs are uncommon but have been reported in some individuals. Death often occurs early due to severe skin infection.

Genetic profile

Harlequin fetus (HF) is inherited as an autosomal recessive condition. As such, a child must inherit two copies of the HF gene in order to be affected. The presence of one HF gene and one normal gene is consistent with being a gene carrier. Carriers are normal but face a risk of having an affected child with another HF carrier. This risk is 25%, or a one in four chance, that two carriers will each pass on an HF gene to his or her offspring. This risk applies to each pregnancy two carriers have together. Conversely, there is also a 75% chance that two carriers would have an unaffected child.

A gene for harlequin fetus has not yet been identified. It has been speculated that this condition actually represents a varied group of genetic abnormalities, all of which cause a similar clinical picture. This is possible given the number of steps involved in keratinization. If so, it is likely that a different abnormal gene is present in different families.

Demographics

According to the Foundation for Ichthyosis and Related Skin Types (F.I.R.S.T.), harlequin fetus is a very rare form of congenital ichthyosis. There is limited data available to provide a specific incidence figure. However, F.I.R.S.T. provides one estimate as approximately one in every 200,000 individuals. Like other autosomal recessive conditions, HF has been observed more often among the children of consanguineous, or related, couples, such as first cousins, etc. Biologically related individuals are much more likely to carry the same recessive gene and, hence, have offspring with autosomal recessive disorders. Children with HF have, however, also been born to unrelated parents.

Signs and symptoms

Infants affected with harlequin ichthyosis have a striking and unique appearance at birth. Their skin is unusually thick, off-white in color, with deep, moist cracks running in different directions. The facial appearance is distorted with marked ectropion, or turning outward (eversion) of the eyelids. The lips also appear to be

turned outward. This is referred to as eclabium. The external ears are absent or flattened against the side of the head. The hands and feet are also grayish-white in color. The fingers and toes appear malformed, in part due to the thick scale that surrounds them but probably also due to interference with blood flow to the digits from the constrictions. Nails and body hair may be missing. There is limited mobility of arms and legs.

A consistent pattern of associated internal abnormalities has not been identified in infants with HF. However, abnormalities of the central nervous system, kidneys, and lungs have been described in some affected individuals. Short stature has been observed in those infants who have survived the newborn period.