Harlequin Syndrome

Congenital skin disease in which the skin builds up and scales (“fish skin disease”). Associated with a very poor prognosis (usually death if infant is younger than 1 week).

Harlequin Fetus; Harlequin-Type Ichthyosis.

First reported in the diary of the Reverend O. Hart in 1750. Inheritable disorder of keratinization caused by a structural defect of tonofibrils (abnormal alpha-protein structure of keratin). This lesion is distinct from the lamellar exfoliative type of congenital ichthyosis, the prognosis of which is better.

Rare (three cases per year in the United Kingdom). Harlequin syndrome is one of the four reported genetic disorders of keratinization displaying a structural defect of tonofibrils; the other three are bullous (or congenital) ichthyosiform erythroderma, Curth-Macklin form of ichthyosis hystrix, and ichthyosis hystrix gravior.

Autosomal recessive. Chromosome 18 might carry the gene responsible for the disorder (transglutaminase 1 [TGM1]). Prenatal diagnosis is available (skin biopsies of the fetus).

In the harlequin fetus, an abnormal radiographic diffraction pattern of the horn material points to a cross-beta-protein structure instead of the normal alpha-protein structure of keratin. A suggested cause for this finding is an abnormality of keratinization.

Characteristic clinical picture. Skin biopsy demonstrating severe cornification. Mutations in TGM1 are identified by sequence analysis of complementary DNA isolated from a fresh 2-mm skin punch biopsy.

Many are stillborn. Others are of low birth weight for dates and, as a rule, die in less than 1 week as a consequence of severe restriction of chest movement and abdomen incompatible with respiration and feeding. Thermoregulation disorders. Plaques, measuring up to 4 or 5 cm per side, have a diamond-like configuration resembling the suit of a harlequin clown. One patient survived 6 years with considerable failure to thrive, probably related to the enormous losses of protein in desquamated skin.

In practice, because of the severity of the disease, harlequin syndrome patients are not eligible for surgery and anesthesia. Assess the severity of the disease, particularly in regard to the thoracic and abdominal involvement. Limit skin desiccation by providing continuous warm humidification of the baby. Assess nutritional state. Exclude the presence of hypovolemia caused by poor feeding. Check core temperature since hypothermia is often present. Investigations: hemoglobin, arterial blood gas analysis, serum protein, and albumin levels.

Venous access is often difficult. Strict aseptic measures must be taken for venous cannulation because the impaired skin barrier is predisposed to infection. Secure the venous cannulas with petroleum jelly gauze and tie or suture down. Adhesive tape likely will denude the skin and cause bleeding. ECG monitoring may require needle electrodes or pads without adhesive for the same reason. Semiflexed rigid limbs require careful positioning to prevent pressure sores. Severe ectropion and bulging eyes require ointment and careful taping to prevent ocular injury. Measures to maintain normothermia should be instituted. Involvement of the chest and abdomen that interferes with respiration ...