Ichthyosis, Harlequin

The harlequin-type designation comes from both the baby's apparent facial expression and the diamond-shape of the scales, which are caused by severe hyperkeratosis. 17th century entertainers known as jesters, or harlequins, wore costumes with diamond patterns on them, as well as a particular style of face paint. The features of the harlequin fetus mimic this stylized makeup, and their faces are often pulled tight into grim parodies of a clown's smile. Each year, more than 16,000 babies are born with some form of ichthyosis; harlequin ichthyosis is one of the rarest types.

The underlying genetic and biochemical abnormalities that result in harlequin ichthyosis are not yet completely understood. Though in 2005, the cause of harlequin ichthyosis was traced to the ABCA12 gene.   The ABCA12 gene is believed to encode a transporter protein involved in the transport of epidermal lipids across cell membranes.  Identification of this gene has made DNA-based prenatal diagnosis of harlequin ichthyosis possible.  In order to express the disorder, individuals must inherit two recessive genes, one from each parent, but the parents (the "carriers") show no signs.

In harlequin infants, premature birth is typical, leaving infants at risk for additional complications from early delivery. In addition to these they may also have

• Severely thickened skin with large, shiny plates of hyperkeratotic scale at birth. Deep, erythematous fissures separate the scales.
• Severe ectropion is present. The free edges of the upper and lower eyelids are everted, leaving the conjunctivae at risk for desiccation and trauma.
• The pinnae may be small and rudimentary or absent.
• Severe traction on the lips causes eclabium and a fixed, open mouth. This may result in feeding difficulties.
• Nasal hypoplasia and eroded nasal alae may occur.
• The limbs are encased in the thick, hyperkeratotic skin, resulting in flexion contractures of the arms, the legs, and the digits. Limb motility is poor to absent. Circumferential constriction of a limb can occur, leading to distal swelling or even gangrene. Hypoplasia of the fingers, toes, and fingernails is reported. Polydactyly is described.
• Thickened skin prevents normal sweat gland function and heat loss. The infants are heat intolerant and can become hyperthermic.
• Restriction of chest-wall expansion can result in respiratory distress, hypoventilation, and respiratory failure.
• Dehydration from excess water loss can cause tachycardia and poor urine output.
• Metabolic abnormalities can cause seizures. CNS depression can be a sign of sepsis or hypoxia. Hyperkeratosis may restrict spontaneous movements, making neurologic assessment difficult.

In the past, harlequin infants rarely survived the first few days of life.  However, with recent advances in neonatal care and perhaps with the administration of systemic retinoids(i.e etretinate) harlequin infants can survive. Retinoids bind to specific retinoic acid receptors and regulate gene transcription. They influence keratinocyte differentiation, normalize abnormal keratinocyte proliferation, and mediate desquamation of hyperkeratotic scale.

Acitretin, a carboxylic acid derivative of etretinate, is the retinoid most commonly prescribed in neonates with harlequin ichthyosis. Isotretinoin has also been used in harlequin ichthyosis. Treatment period varies from months to several years and it may be required indefinitely to prevent relapse. Treatment may also involve a life-saving ritual of scrubbing, bathing and creaming to keep the skin growth under control.