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.

Signs and Symptoms

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 mutation in each cell. This mutation can disrupt how information in the IKBKAP gene is spliced together to make a blueprint for the production of IKAP protein. As a result of this splicing 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.

Read more about the IKBKAP gene.

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.

What other names do people use for familial dysautonomia?

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

External Links

Where can I find information about treatment for familial dysautonomia?

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

• Gene Review: Familial Dysautonomia
• MedlinePlus Encyclopedia: Riley-Day Syndrome

You might also find information on treatment of familial dysautonomia in Educational resources and Patient support.

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.

• MedlinePlus - Health information (4 links)
• Additional NIH Resources - National Institutes of Health
• National Institute of Neurological Disorders and Stroke: Information Page
• Educational resources - Information pages (9 links)
• Patient support - For patients and families (6 links)

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

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• Genetic Tools - Teaching cases
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• OMIM - Genetic disorder catalog

See How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about familial dysautonomia?

• See How can I find a genetics professional in my area? in the Handbook.
• Ask the Genetic and Rare Diseases Information Center.
• Submit your question to Ask the Geneticist.

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

• What does it mean if a disorder seems to run in my family?
• What are the different ways in which a genetic condition can be inherited?
• If a genetic disorder runs in my family, what are the chances that my children will have the condition?
• Why are some genetic conditions more common in particular ethnic groups?

These links provide additional genetics resources that may be useful.

• Genetics and health
• Resources for Patients and Families
• Resources for Health Professionals

What glossary definitions help with understanding familial dysautonomia?

Ashkenazi Jewish ; atrophy ; autonomic nervous system ; autosomal ; autosomal recessive ; cell ; class ; cyanosis ; developmental delay ; digestion ; fainting ; familial ; gene ; hypotension ; hypotonia ; infection ; involuntary ; kidney ; learning disability ; muscle tone ; mutation ; nerve cell ; nervous system ; neuropathy ; optic nerve ; orthostatic ; perception ; population ; protein ; recessive ; scoliosis ; sensitivity ; sign ; splicing ; symptom ; syndrome

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. PubMed citation
• Axelrod FB, Hilz MJ. Inherited autonomic neuropathies. Semin Neurol. 2003 Dec;23(4):381-90. Review. PubMed citation
• Axelrod FB. Familial dysautonomia. Muscle Nerve. 2004 Mar;29(3):352-63. Review. PubMed citation
• Axelrod FB. Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other HSANs. Clin Auton Res. 2002 May; 12 Suppl 1: I2-14. Review. No abstract available. PubMed citation
• 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. PubMed citation
• 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. No abstract available. PubMed citation
• 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. PubMed citation
• Slaugenhaupt SA, Gusella JF. Familial dysautonomia. Curr Opin Genet Dev. 2002 Jun;12(3):307-11. Review. PubMed citation