National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Harlequin syndrome


Other Names:
Unilateral loss of facial flushing and sweating with contralateral anhidrosis; Sudden onset of unilateral flushing and sweating; Progressive isolated segmental anhidrosis
Categories:
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] 
Last updated: 8/1/2017
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]
Last updated: 8/1/2017
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] 
Last updated: 8/1/2017
Harlequin syndrome does not appear to be inherited from one generation to the next. In most cases, Harlequin syndrome is thought to be caused by injury to the nerve bundles, which cannot be inherited from a parent. However, in some cases Harlequin syndrome seems to be associated with autoimmune disease, which could be caused by the immune system attacking the nerve bundles as if they were an infection.[4]

In general, autoimmune diseases are thought to be caused by a combination of genetic and environmental factors. If Harlequin syndrome is caused by an autoimmune response, it is possible that the symptoms of Harlequin syndrome could occur in other members of the family with an autoimmune disease.
Last updated: 8/1/2017
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] 
Last updated: 8/1/2017
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]
Last updated: 8/1/2017
The long-term outlook for people affected by Harlequin syndrome is good. This syndrome is known as a benign condition because it is not known to affect a person’s daily living or lifespan.[4] However, for some people the facial flushing and sweating associated with Harlequin syndrome may be embarrassing. These individuals may desire treatment.[9]

It is important to determine if there is another underlying cause of the symptoms in order to receive proper treatment and accurately predict a person’s long-term outlook.[6]
Last updated: 8/1/2017

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Harlequin syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Harlequin syndrome:
    The National Registry for Ichthyosis & Related Skin Disorders
     

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

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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My daughter was diagnosed with Harlequin syndrome as an infant. At first the frequency of her face getting flush would be rare, however now that she is a lot more active it seems to happen more, and she does not have to be doing anything as far as activity goes. Will this continue to the point that her face will never be plain? Is it possible that she feels it? She will lightly hit her face sometimes as is starts to get red. Is there a treatment? How rare is this? Is it genetic or is it a development of nerves as she grew in my womb? See answer


  1. Harlequin syndrome. Orphanet. http://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. http://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. http://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. http://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/.