Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Paroxysmal extreme pain disorder

Reviewed November 2012

What is paroxysmal extreme pain disorder?

Paroxysmal extreme pain disorder is a condition characterized by skin redness and warmth (flushing) and attacks of severe pain in various parts of the body. The area of flushing typically corresponds to the site of the pain. The pain attacks experienced by people with paroxysmal extreme pain disorder usually last seconds to minutes, but in some cases can last hours. These attacks can start as early as infancy. Early in life, the pain is typically concentrated in the lower part of the body, especially around the rectum, and is usually triggered by a bowel movement. Some children may develop constipation, which is thought to be due to fear of triggering a pain attack. Pain attacks in these young children may also be accompanied by seizures, slow heartbeat, or short pauses in breathing (apnea).

As a person with paroxysmal extreme pain disorder ages, the location of pain changes. Pain attacks switch from affecting the lower body to affecting the head and face, especially the eyes and jaw. Triggers of these pain attacks include changes in temperature (such as a cold wind) and emotional distress as well as eating spicy foods and drinking cold drinks.

Paroxysmal extreme pain disorder is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.

How common is paroxysmal extreme pain disorder?

Paroxysmal extreme pain disorder is a rare condition; approximately 80 affected individuals have been described in the scientific literature.

What genes are related to paroxysmal extreme pain disorder?

Mutations in the SCN9A gene cause paroxysmal extreme pain disorder. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.

The SCN9A gene mutations that cause paroxysmal extreme pain disorder result in NaV1.7 sodium channels that do not close completely when it is turned off, allowing sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the pain attacks experienced by people with paroxysmal extreme pain disorder. It is unknown why the pain attacks associated with this condition change location over time or what causes the other features of this condition such as seizures and changes in breathing.

Related Gene(s)

Changes in this gene are associated with paroxysmal extreme pain disorder.

  • SCN9A

How do people inherit paroxysmal extreme pain disorder?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person has one parent with the condition.

Where can I find information about diagnosis or management of paroxysmal extreme pain disorder?

These resources address the diagnosis or management of paroxysmal extreme pain disorder and may include treatment providers.

  • Genetic Testing Registry: Paroxysmal extreme pain disorder (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1833661)

You might also find information on the diagnosis or management of paroxysmal extreme pain disorder in Educational resources (http://www.ghr.nlm.nih.gov/condition/paroxysmal-extreme-pain-disorder/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/paroxysmal-extreme-pain-disorder/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about paroxysmal extreme pain disorder?

You may find the following resources about paroxysmal extreme pain disorder helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for paroxysmal extreme pain disorder?

  • familial rectal pain
  • PEPD
  • PEXPD
  • submandibular, ocular, and rectal pain with flushing

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about paroxysmal extreme pain disorder?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding paroxysmal extreme pain disorder?

apnea ; autosomal ; autosomal dominant ; cell ; channel ; constipation ; familial ; gene ; inherited ; ions ; nervous system ; neuropathy ; nociceptors ; peripheral ; peripheral nervous system ; peripheral neuropathy ; rectum ; sodium ; sodium channel ; subunit

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Dabby R. Pain disorders and erythromelalgia caused by voltage-gated sodium channel mutations. Curr Neurol Neurosci Rep. 2012 Feb;12(1):76-83. doi: 10.1007/s11910-011-0233-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21984269?dopt=Abstract)
  • Estacion M, Han C, Choi JS, Hoeijmakers JG, Lauria G, Drenth JP, Gerrits MM, Dib-Hajj SD, Faber CG, Merkies IS, Waxman SG. Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of NaV1.7. Mol Pain. 2011 Dec 2;7:92. doi: 10.1186/1744-8069-7-92. (http://www.ncbi.nlm.nih.gov/pubmed/22136189?dopt=Abstract)
  • Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, Ostman J, Klugbauer N, Wood JN, Gardiner RM, Rees M. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron. 2006 Dec 7;52(5):767-74. (http://www.ncbi.nlm.nih.gov/pubmed/17145499?dopt=Abstract)
  • Fertleman CR, Ferrie CD, Aicardi J, Bednarek NA, Eeg-Olofsson O, Elmslie FV, Griesemer DA, Goutières F, Kirkpatrick M, Malmros IN, Pollitzer M, Rossiter M, Roulet-Perez E, Schubert R, Smith VV, Testard H, Wong V, Stephenson JB. Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). Neurology. 2007 Aug 7;69(6):586-95. (http://www.ncbi.nlm.nih.gov/pubmed/17679678?dopt=Abstract)
  • Fischer TZ, Waxman SG. Familial pain syndromes from mutations of the NaV1.7 sodium channel. Ann N Y Acad Sci. 2010 Jan;1184:196-207. doi: 10.1111/j.1749-6632.2009.05110.x. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20146699?dopt=Abstract)
  • Lampert A, O'Reilly AO, Reeh P, Leffler A. Sodium channelopathies and pain. Pflugers Arch. 2010 Jul;460(2):249-63. doi: 10.1007/s00424-009-0779-3. Epub 2010 Jan 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20101409?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2012
Published: December 16, 2014