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Disease Profile

Harlequin syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

All ages

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ICD-10

G90.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Unilateral loss of facial flushing and sweating with contralateral anhidrosis; Sudden onset of unilateral flushing and sweating; Progressive isolated segmental anhidrosis

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Harlequin syndrome is a syndrome affecting the autonomic nervous system.[1] The autonomic nervous system is responsible for controlling the body’s natural processes such as sweating, skin flushing, and the response of the pupils to stimuli.[2] People with Harlequin syndrome have the absence of sweating and flushing of skin on one side of the body (unilateral), especially of the face, arms, and chest.[1][3]

The symptoms associated with Harlequin syndrome may be more likely to occur when a person has been exercising, is very warm, or is in an intense emotional situation.[1] In these situations, one side of the body sweats and flushes appropriately as a response to the situation, whereas the other side of the body does not. The asymmetrical facial sweating and flushing associated with this condition has been named the “Harlequin sign.” Harlequin syndrome is thought to be one of a spectrum of diseases that can cause Harlequin sign.[4]

The exact cause of Harlequin syndrome is not completely understood. In some patients with this syndrome, the underlying cause seems to be a lesion or tumor that is affecting the ability of the cells of the autonomic nervous system to communicate with one side of the body.[4] However, in many cases an exact cause of the symptoms is not found.[5]

Diagnosis of Harlequin syndrome is based on observing symptoms consistent with the syndrome, followed by a series of tests to rule out other diseases associated with Harlequin sign.[4][5] Treatment may consist of removing any lesion that may be causing the symptoms of the syndrome. If no lesion is present and the syndrome is not interfering with a person’s daily living, treatment may not be necessary.[6]

Symptoms

Harlequin syndrome may be associated with warmth on the flushed side of the body and lack of sweating (anhidrosis) on the opposite side of the body (contralateral side). The signs and symptoms of Harlequin syndrome may begin at any age and have been reported in children or from birth in some cases.[7][8] Symptoms may be caused by exercise, heat, spicy foods, or intense emotional situations.[1][6]

Some people with the Harlequin sign may have other symptoms including cluster headaches, tearing of the eyes, nasal discharge, forehead sweating, abnormal contraction of the pupils, and drooping of the upper eyelid (ptosis). There is some debate whether or not these symptoms are related to Harlequin syndrome or if they may be associated with another disease.[4] Signs and symptoms of Harlequin syndrome may overlap with those of Ross syndrome, Aide syndrome, and Horner’s syndrome.[4]

Cause

Most cases of Harlequin syndrome are thought to occur when nerve bundles, particularly ones in the head and neck, are injured. Nerve bundles allow signals from the autonomic nervous system to travel throughout the body. In many cases, the cause of the injury to the nerve bundles is unknown.[5] However, individual causes of the symptoms of Harlequin syndrome have been reported in association with: trauma, tumor, stroke, autoimmune disease (multiple sclerosis or hyperthyroidism), a virus, or a fluid-filled cyst in the spinal cord (syrinx).[4][9][10] 

When the nerve bundles are injured, they are not able to communicate with half of the face and body properly. Therefore, that half of the body is not able to respond to stimuli such as exercise by flushing and producing sweat. This causes the Harlequin sign that is associated with this syndrome.[4] 

Diagnosis

A diagnosis of Harlequin syndrome is typically made when a person has symptoms consistent with the condition. This may include clinical evaluation after exercise and a sweating test to determine which parts of the body are affected.[8]

If Harlequin syndrome is suspected, other tests may be ordered to rule out other symptoms associated with the syndrome or other diseases with similar symptoms. These tests may include an MRI of the spine and brain to determine if there is a visible cause of the symptoms.[4] Doctors may also want to see if there are any symptoms affecting the pupils of the eyes and the reflexes elsewhere in the body.[5] 

Treatment

If an underlying cause of Harlequin syndrome is identified, treatment should be directed to the cause of the syndrome. Surgery may be possible to repair a lesion that is causing Harlequin syndrome. If there is no known cause of the symptoms and the symptoms are not affecting a person’s daily life, some people may choose not to pursue any treatment.[6]

In cases where an individual has symptoms of Harlequin syndrome and wishes to receive treatment, injection with botulinum toxin (Botox) or a procedure called contralateral sympathectomy is possible.[5][8][9] In contralateral sympathectomy, the nerve bundles that are responsible for causing flushing in the face are interrupted. Therefore, this procedure causes both sides of the face to no longer flush or sweat. Because the symptoms of Harlequin syndrome are not typically associated with affecting a person’s daily life, this treatment is only recommended if a person is very uncomfortable with the flushing and sweating associated with the syndrome.[9]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Social Networking Websites

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Harlequin syndrome. Click on the link to view a sample search on this topic.

References

  1. Harlequin syndrome. Orphanet. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199282. Accessed 7/24/2017.
  2. McDougal DH and Gamlin PD. Autonomic control of the eye. Comprehensive Physiology. January 2015; 5(1):439-473. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919817/.
  3. Corbett M and Abernethy DA. Harlequin syndrome. J Neurol Neurosurg Psychiatry. 1999; 66(4):544. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1736279/pdf/v066p00544.pdf.
  4. Tascilar N, Tekin NS, Erdem Z, Alpay A, and Emre U. Unnoticed dysautonomic syndrome of the face: Harlequin syndrome. Autonomic Neuroscience: Basic and Clinical. December 30, 2007; 137(1-2):1-3. https://www.ncbi.nlm.nih.gov/pubmed?term=17569597.
  5. Biondi A, Persiani R, Zoccali M, Rausei S, Cananzi F, and D'Ugo D.. Harlequin syndrome. Ann Thorac Surg. July 2009; 88(1):304. https://www.annalsthoracicsurgery.org/article/S0003-4975(08)02061-4/fulltext.
  6. Fallon KE and May JJ. Harlequin syndrome in two athletes. Br J Sports Med. 2005; 39:e1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1725016/pdf/v039p000e1.pdf.
  7. Pavone P, Praticò AD, Micali G, Greco F, Ruggieri M, and Pavone L. Autonomic Dysfunction Manifesting With Asymmetric Face Flushing and Paroxysmal Nonconvulsive Episodes. J Child Neurol. December 2013; 28(12):1673-1676. https://www.ncbi.nlm.nih.gov/pubmed?term=23112241.
  8. Algahtani H, Shirah B, Algahtani R, and Alkahtani A. Idiopathic Harlequin syndrome manifesting during exercise: A case report and review of the literature. Case Reports in Medicine. 2017; 2017:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339527/.
  9. de Avelar Breunig J, Hartmann M, Freire CF, and de Almeida HL. Harlequin syndrome in childhood—case report. Anais Brasileiros de Dermatologia. November-December 2012; 87(6):907-909. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699916/.
  10. Pradeep PV, Benede AK, Harshita SS, and Jayashree B. Harlequin syndrome in a case of toxic goiter: a rare association. Case Reports in Medicine. 2011; 2011:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139896/.

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