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Genetics Home Reference: your guide to understanding genetic conditions
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Familial dysautonomia

Reviewed August 2013

What is familial dysautonomia?

Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.

Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.

Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain.

How common is familial dysautonomia?

Familial dysautonomia occurs primarily in people of Ashkenazi (central or eastern European) Jewish descent. It affects about 1 in 3,700 individuals in Ashkenazi Jewish populations. Familial dysautonomia is extremely rare in the general population.

What genes are related to familial dysautonomia?

Mutations in the IKBKAP gene cause familial dysautonomia.

The IKBKAP gene provides instructions for making a protein called IKK complex-associated protein (IKAP). This protein is found in a variety of cells throughout the body, including brain cells.

Nearly all individuals with familial dysautonomia have two copies of the same IKBKAP gene mutation in each cell. This mutation can disrupt how information in the IKBKAP gene is pieced together to make a blueprint for the production of IKAP protein. As a result of this error, a reduced amount of normal IKAP protein is produced. This mutation behaves inconsistently, however. Some cells produce near normal amounts of the protein, and other cells—particularly brain cells—have very little of the protein. Critical activities in brain cells are probably disrupted by reduced amounts or the absence of IKAP protein, leading to the signs and symptoms of familial dysautonomia.

Related Gene(s)

Changes in this gene are associated with familial dysautonomia.

  • IKBKAP

How do people inherit familial dysautonomia?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of familial dysautonomia?

These resources address the diagnosis or management of familial dysautonomia and may include treatment providers.

  • Gene Review: Familial Dysautonomia (http://www.ncbi.nlm.nih.gov/books/NBK1180)
  • Genetic Testing Registry: Familial dysautonomia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0013364)
  • MedlinePlus Encyclopedia: Riley-Day Syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001387.htm)

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

You may find the following resources about familial dysautonomia 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 familial dysautonomia?

  • FD
  • HSAN3
  • HSAN Type III
  • HSN-III
  • Riley-Day Syndrome

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 familial dysautonomia?

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

What glossary definitions help with understanding familial dysautonomia?

Ashkenazi Jewish ; atrophy ; autonomic nervous system ; autosomal ; autosomal recessive ; cell ; cyanosis ; developmental delay ; digestion ; disabilities ; fainting ; familial ; gene ; hereditary ; hypotension ; hypotonia ; inherited ; involuntary ; kidney ; muscle tone ; mutation ; nervous system ; neuropathy ; orthostatic ; perception ; population ; protein ; recessive ; scoliosis ; sensitivity ; syndrome

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

References

  • Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY. Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet. 2001 Mar;68(3):753-8. Epub 2001 Jan 22. (http://www.ncbi.nlm.nih.gov/pubmed/11179021?dopt=Abstract)
  • Axelrod FB, Hilz MJ. Inherited autonomic neuropathies. Semin Neurol. 2003 Dec;23(4):381-90. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15088259?dopt=Abstract)
  • Axelrod FB. Familial dysautonomia. Muscle Nerve. 2004 Mar;29(3):352-63. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14981733?dopt=Abstract)
  • Axelrod FB. Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other HSANs. Clin Auton Res. 2002 May;12 Suppl 1:I2-14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12102459?dopt=Abstract)
  • Carroll MS, Kenny AS, Patwari PP, Ramirez JM, Weese-Mayer DE. Respiratory and cardiovascular indicators of autonomic nervous system dysregulation in familial dysautonomia. Pediatr Pulmonol. 2012 Jul;47(7):682-91. doi: 10.1002/ppul.21600. Epub 2011 Dec 13. (http://www.ncbi.nlm.nih.gov/pubmed/22170819?dopt=Abstract)
  • Elkayam L, Matalon A, Tseng CH, Axelrod F. Prevalence and severity of renal disease in familial dysautonomia. Am J Kidney Dis. 2006 Nov;48(5):780-6. (http://www.ncbi.nlm.nih.gov/pubmed/17059997?dopt=Abstract)
  • Gold-von Simson G, Axelrod FB. Familial dysautonomia: update and recent advances. Curr Probl Pediatr Adolesc Health Care. 2006 Jul;36(6):218-37. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16777588?dopt=Abstract)
  • Norcliffe-Kaufmann L, Axelrod FB, Kaufmann H. Developmental abnormalities, blood pressure variability and renal disease in Riley Day syndrome. J Hum Hypertens. 2013 Jan;27(1):51-5. doi: 10.1038/jhh.2011.107. Epub 2011 Dec 1. (http://www.ncbi.nlm.nih.gov/pubmed/22129610?dopt=Abstract)
  • Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins C, Makalowska I, Brownstein M, Krappmann D, Scheidereit C, Maayan C, Axelrod FB, Gusella JF. Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Hum Genet. 2001 Mar;68(3):598-605. Epub 2001 Jan 22. (http://www.ncbi.nlm.nih.gov/pubmed/11179008?dopt=Abstract)
  • Slaugenhaupt SA, Gusella JF. Familial dysautonomia. Curr Opin Genet Dev. 2002 Jun;12(3):307-11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12076674?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: August 2013
Published: September 15, 2014