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At a glance

Harlequin Syndrome is a condition characterized by asymmetric sweating and flushing on the upper thoracic region of the chest, the neck, and the face. It is usually associated with an injury sustained to the sympathetic nervous system. It can also be the result of a unilateral endoscopic thoracic sympathectomy (ETS) or endoscopic sympathetic blockade (ESB) caused by surgery. This medical condition may also feature dermatological alteration leading to scales development (“fish skin disease”). Horner Syndrome, another problem associated with lesions to the sympathetic nervous system, is often seen in conjunction with Harlequin Syndrome. Associated with a very poor prognosis in which infants die usually younger than 1 week of age.

Synonyms

Harlequin Fetus; Harlequin-Type Ichthyosis.

History

First reported in the diary of the Reverend O. Hart in 1750. The name for the syndrome is credited to J.W. Lance and P.D. Drummond who were inspired by resemblance patient’s half-flushed faces bore to colorful Harlequin masks.

Incidence

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. It affects fewer than 200,000 people in the United States.

Genetic inheritance

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

Pathophysiology

One possible cause of Harlequin Syndrome is a lesion to the preganglionic or postganglionic cervical sympathetic fibers and parasympathetic neurons of the ciliary ganglion. It is also believed that torsion of the thoracic spine can cause blockage of the anterior radicular artery leading to Harlequin Syndrome. The sympathetic deficit on the denervated side causes the flushing of the opposite side to appear more pronounced. 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.

Diagnosis

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

Clinical aspects

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. ...

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