Familial dysautonomia

Title

Other Names:

Dysautonomia, familial; FD; Hereditary sensory neuropathy type 3; Dysautonomia, familial; FD; Hereditary sensory neuropathy type 3; Hereditary sensory and autonomic neuropathy 3; HSAN 3; HSN 3; Riley Day syndrome See More

Categories:

Congenital and Genetic Diseases; Eye diseases; Nervous System Diseases; Congenital and Genetic Diseases; Eye diseases; Nervous System Diseases; Skin Diseases See More

This disease is grouped under:

Hereditary sensory and autonomic neuropathy; Primary orthostatic hypotension

Summary Summary

Familial dysautonomia (FD) affects nerve cells in the autonomic nervous system, the part of the nervous system that controls involuntary functions like breathing and digestion. The symptoms of FD are present at birth and include difficulty swallowing, and poor control of blood pressure, body temperature and breathing. Other symptoms may include the inability to make tears or feel pain, vomiting episodes, frequent pneumonia, and difficulty walking. Over time, the symptoms of FD tend to get worse and are often life-threatening. FD is caused by genetic variations in the ELP1 gene, and is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, clinical exam, and the results of genetic testing. Treatment is focused on managing the symptoms.^[1]^[2]^[3]

Last updated: 9/16/2020

Symptoms Symptoms

The following list includes the most common signs and symptoms in people with familial dysautonomia. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms of familial dysautonomia include:^[1]^[3]

Difficulty swallowing and feeding
Low muscle tone (hypotonia)
Absence of tears
Poor control of breathing, especially during sleep
Trouble regulating blood pressure and body temperature
Insensitivity to pain
Unsteady gait
Vomiting episodes
Frequent pneumonia

Symptoms of familial dysautonomia are present at birth. Over time, symptoms tend to get worse. Some people with FD develop curvature of the spine (scoliosis), kidney problems and lung damage. FD is considered a severe condition, and often results in a shortened lifespan.^[1]^[3]^[4]

Last updated: 9/16/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormal pupil morphology	Abnormality of the pupil Pupillary abnormalities Pupillary abnormality [ more ]	0000615
Alacrima	Absence of tears in the eyes Absent tear secretion [ more ]	0000522
EMG abnormality		0003457
Feeding difficulties in infancy		0008872
Growth delay	Delayed growth Growth deficiency Growth failure Growth retardation Poor growth Retarded growth [ more ]	0001510
Hyperhidrosis	Excessive sweating Increased sweating Profuse sweating Sweating Sweating profusely Sweating, increased [ more ]	0000975
Hypohidrosis	Decreased ability to sweat Decreased sweating Sweating, decreased [ more ]	0000966
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Impaired pain sensation	Decreased pain sensation	0007328
Malignant hyperthermia		0002047
Orthostatic hypotension	Decrease in blood pressure upon standing up	0001278
30%-79% of people have these symptoms
Ataxia		0001251
Behavioral abnormality	Behavioral changes Behavioral disorders Behavioral disturbances Behavioral problems Behavioral/psychiatric abnormalities Behavioural/Psychiatric abnormality Psychiatric disorders Psychiatric disturbances [ more ]	0000708
Corneal erosion	Damage to outer layer of the cornea of the eye	0200020
Gait disturbance	Abnormal gait Abnormal walk Impaired gait [ more ]	0001288
Hypertension		0000822
Muscular hypotonia	Low or weak muscle tone	0001252
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Scoliosis		0002650
5%-29% of people have these symptoms
Abnormal pleura morphology		0002103
Abnormality of the peritoneum		0002585
Acrocyanosis	Persistent blue color of hands, feet, or parts of face	0001063
Avascular necrosis	Death of bone due to decreased blood supply	0010885
Corneal opacity		0007957
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Glomerulopathy		0100820
Heterochromia iridis	Different colored eyes	0001100
Hyponatremia	Low blood sodium levels	0002902
Myopia	Close sighted Near sighted Near sightedness Nearsightedness [ more ]	0000545
Optic atrophy		0000648
Osteolysis	Breakdown of bone	0002797
Recurrent fractures	Increased fracture rate Increased fractures Multiple fractures Multiple spontaneous fractures Varying degree of multiple fractures [ more ]	0002757
Renal insufficiency	Renal failure Renal failure in adulthood [ more ]	0000083
Seizure		0001250
Tachycardia	Fast heart rate Heart racing Racing heart [ more ]	0001649
Percent of people who have these symptoms is not available through HPO
Abnormal renal physiology	Abnormal kidney function Kidney function issue [ more ]	0012211
Autosomal recessive inheritance		0000007
Congenital onset	Symptoms present at birth	0003577
Constipation		0002019
Corneal ulceration		0012804
Decreased corneal reflex		0008000
Decreased number of large peripheral myelinated nerve fibers		0003387
Decreased sensitivity to hypoxemia		0005947
Diarrhea	Watery stool	0002014
Elevated serum creatinine	Elevated creatinine High blood creatinine level Increased creatinine Increased serum creatinine [ more ]	0003259
Emotional lability	Emotional instability	0000712
Episodic hyperhidrosis	Sporadic excessive sweating	0001069
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Glomerulosclerosis		0000096
Hypogeusia	Decreased taste Decreased taste sensation [ more ]	0000224
Incoordination	Difficulties in coordination Incoordination of limb movements Limb incoordination [ more ]	0002311
Increased blood urea nitrogen		0003138
Neuropathic arthropathy		0002821
Progressive	Worsens with time	0003676
Recurrent corneal erosions	Recurrent breakdown of clear protective layer of eye	0000495
Recurrent fever	Episodic fever Increased body temperature, episodic Intermittent fever [ more ]	0001954
Recurrent infections due to aspiration		0004891
Vomiting	Throwing up	0002013

Showing of 58 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 11/1/2020

Cause Cause

Familial dysautonomia is caused by the ELP1 gene not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[3]

Last updated: 9/16/2020

Inheritance Inheritance

Familial dysautonomia is inherited in an autosomal recessive pattern.^[3] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be altered to have the condition.

People with autosomal recessive conditions inherit one alteration from each of their parents. The parents, who each have one gene alteration, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Last updated: 9/16/2020

Diagnosis Diagnosis

Familial dysautonomia is diagnosed based on the symptoms, clinical exam, and confirmed by the results of genetic testing.^[2]^[3]

Last updated: 9/16/2020

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

Treatment for familial dysautonomia (FD) is focused on managing the symptoms. Treatment options include medications to help manage blood pressure, breathing problems, and vomiting episodes. Some people with FD need a feeding tube due to swallowing problems. In addition, in some people, surgery is necessary to correct curvature of the spine.^[1]^[4]

Specialists involved in the care of someone with familial dysautonomia may include:

Neurologist
Gastroenterologist
Otolaryngologist (ear, nose, and throat doctor)
Pulmonologist
Ophthalmologist
Sleep specialist

Last updated: 9/16/2020

Management Guidelines

Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Statistics Statistics

Familial dysautonomia mainly impacts people of eastern European (Ashkenazi) Jewish descent. It has been estimated that FD occurs in about one in 10,000 live births in North America. The incidence of FD has been decreasing over time due to prenatal screening and testing.^[1]

Last updated: 9/16/2020

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN). Normal or increased sweating easily distinguishes familial dysautonomia (FD) from HSAN4, also hypertensive crises are unique to FD and not present in other HSANs. Deep tendon reflexes are absent in FD. Visit the Orphanet disease page for more information.

Research Research

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.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Familial dysautonomia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.
The RDCRN - Autonomic Disorders Consortium is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with many types of autonomic disorders through research.

Patient Registry

The Inherited Neuropathies Consortium is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with Charcot Marie Tooth disease through research. The Inherited Neuropathies Consortium has a registry for patients who wish to be contacted about clinical research opportunities.

Organizations 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.

Organizations Supporting this Disease

Dysautonomia Information Network
PO Box 10057
Swanzey, NH 03446, NH 03446
E-mail: webmaster@dinet.org
Website: https://www.dinet.org/
Dysautonomia International
P.O. Box 596
East Moriches, NY 11940
E-mail: info@DysautonomiaInternational.org
Website: http://www.dysautonomiainternational.org/
Jewish Genetic Disease Consortium (JGDC)
450 West End Ave., 6A
New York, NY 10024
Toll-free: 866-370-GENE (4363)
Telephone: 855-642-6900
Fax: 212-873-7892
E-mail: info@jewishgeneticdiseases.org
Website: http://www.JewishGeneticDiseases.org
The Foundation for Peripheral Neuropathy
485 Half Day Road
Suite 350
Buffalo Grove, IL 60089
Telephone: +1-877-883-9942
Fax: +1-847-883-9960
E-mail: https://www.foundationforpn.org/contact-us/
Website: https://www.foundationforpn.org

Do you know of an organization? We want to hear from you.

Learn More 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.

Where to Start

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
Genetics Home Reference (GHR) contains information on Familial dysautonomia. This website is maintained by the National Library of Medicine.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
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.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
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 Familial dysautonomia. Click on the link to view a sample search on this topic.

Videos/Presentations

A Positive Exposure program called FRAME has an educational film about Familial dysautonomia that was created to change how medical information is presented to healthcare professionals. FRAME stands for Faces Redefining the Art of Medical Education. Positive Exposure is an organization that uses photography, film, and narrative to transform public perceptions of people living with genetic, physical, intellectual, and behavioral differences.

News & Events News & Events

News

Rare Diseases Are Not Rare - Gallery of Creative Work Raises Awareness of Rare Diseases
September 1, 2020
NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

GARD Answers GARD Answers

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.

Have a question? Contact a GARD Information Specialist.

References References

Norcliffe-Kaufmann L, Slaugenhaupt SA, Kaufmann H. Familial dysautonomia: History, genotype, phenotype and translational research. Prog Neurobiol. 2017; 152:131-148. https://pubmed.ncbi.nlm.nih.gov/27317387.
Rubin BY, Anderson SL. IKBKAP/ELP1 gene mutations: mechanisms of familial dysautonomia and gene-targeting therapies. Appl Clin Genet. 2017; 10:95-103. https://pubmed.ncbi.nlm.nih.gov/29290691.
Shohat M, Weisz Hubshan M. Familial Dysautonomia. GeneReviews. Updated Dec 18, 2014; https://pubmed.ncbi.nlm.nih.gov/20301359.
Kazachkov M, Palma JA, Norcliffe-Kaufmann L, et al. Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations. Respir Med. 2018; 141:37-46. https://pubmed.ncbi.nlm.nih.gov/30053970.