Rare Pediatrics News

Disease Profile

Familial dysautonomia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

G90.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Dysautonomia, familial; FD; Hereditary sensory neuropathy type 3;

Categories

Congenital and Genetic Diseases; Eye diseases; Nervous System Diseases;

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]

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]

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.

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
Glomerular sclerosis
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

Diagnosis

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

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 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

    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.

      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

        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.

              References

              1. 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.
              2. 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.
              3. Shohat M, Weisz Hubshan M. Familial Dysautonomia. GeneReviews. Updated Dec 18, 2014; https://pubmed.ncbi.nlm.nih.gov/20301359.
              4. 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.

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