Skip Navigation LinksHome > Social Action/Advocacy > About Familial Dysautonomia
About Familial Dysautonomia

Also known as:
Riley-Day Syndrome (After the two pediatricians that described the disorder in 1949) and; HSAN III (hereditary sensory and autonomic neuropathy, type III)

Although the public and many medical professionals are unaware of familial dysautonomia, a striking 1 in 30 Ashkenazi Jews are carriers of the more common FD mutation, a prevalence similar to the better known disorder, Tay-Sachs disease. With the identification of the two mutations that cause FD in January, 2001, carrier screening for these mutations are now available. For more information on the identification of the gene responsible for FD and on how you can be tested to see if you are a carrier these mutations, go to What's New at FD Village.

Familial dysautonomia (FD) is an autosomal recessive genetic disorder that affects the autonomic and sensory nervous systems. FD is seen in males and females equally, among Ashkenazi (Eastern European) Jews. Some common features of FD include: the lack of overflow tears while crying; a decreased ability to feel pain or temperature sensations; inappropriate blood pressure and body temperature fluctuations; trouble with feeding, swallowing and gastrointestinal motility; hypotonia; developmental delays; recurrent pneumonias (from aspiration); scoliosis and kyphosis; increased sweating; transient skin blotching; and decreased stature.

Presently, there is no cure for this progressive disorder and treatment is aimed at controlling symptoms and avoiding complications. Survival is increased with treatment, and new research will hopefully continue towards a cure in time to save the lives of the brave children and adults who suffer from familial dysautonomia.

Increased awareness and research in familial dysautonomia will help develop more treatment options and ultimately find a cure. Further insight into FD will also provide help for related sensory and autonomic nervous systems disorders and other commonly seen medical conditions. The medical and scientific community will develop a better understanding of how the body regulates functions such as blood pressure (both hypertension and orthostatic hypotension are seen in FD), pain, body temperature, corneal wound healing, swallowing, reflux and gastrointestinal motility, and nervous system cell death (apoptosis).

How Do I Know If My Child Has Familial Dysautonomia?

At present, familial dysautonomia is officially diagnosed based on the presence of the following set of clinical symptoms.

  •  Lack of tears (some children may be seen to cry a single tear on occasion; this criteria refers to no "overflow" tears with emotional upset or injury)
    Lack of the fungiform papilla on the tongue (these are the red bumps seen mostly on the tip of the tongue. In some younger children or babies, it has been difficult to determine if the papilla are truly there or not. As the child ages, however, it becomes clear that the papilla are missing. Many individuals with familial dysautonomia have a tongue that appears shiny)
  • Lack of an axon flare with histamine testing. The intradermal histamine test is a type of allergy test and is done with a single injection just within the skin. A normal response to a histamine injection under the skin is to have a wheal (raised bump) and a flare (redness). In familial dysautonomia and other neurological conditions, an abnormal response is seen and although the bump becomes evident, rather than the normal diffuse red flare there is a sharp demarcation noted at the wheal.
  • Decreased deep tendon reflexes (knee jerk reflex that a doctor does with the reflex hammer for instance)
  • Both parents of Ashkenazi Jewish heritage

If the diagnosis of familial dysautonomia is suspected despite the absence of one or more of the above, further testing can be done to confirm the diagnosis. In addition to these symptoms, parents may also notice developmental delays, poor weight gain, frequent respiratory infections, transient red blotching of the skin (especially during excitement, eating, or early stages of sleep), problems eating and drinking, reflux, inappropriate responses (decreased) to injury and hot or cold exposure, and excessive sweating. Although the precise location of the mutation has not yet been identified, it is possible (using flanking markers) to confirm the diagnosis with genetic testing. Once a family member is identified to have familial dysautonomia, it is possible to test prenatally and to test for carrier status of other family members and unrelated spouses. If your child or someone you know has some of these symptoms and you suspect that they may have familial dysautonomia, contact the Dysautonomia Treatment and Evaluation Center.


Axelrod, FB
Familial dysautonomia: a 47-year perspective. How technology confirms clinical acumen.
J Pediatr 1998 Mar;132(3 Pt 2):S2-5.
Maayan, C. et al.
Diagnosis and misdiagnosis in familial dysautonomia.
Harefuah 1994 May 15;126(10):565-7.
Kaplan, M, et al.
Diagnosis of familial dysautonomia in the newborn period.
J Pediatr 1988 Jan;112(1):162.
Maayan, C, et al.
Incidence of familial dysautonomia in Israel 1977-1981.
Clin Genet 1987 Aug;32(2):106-8.
Axelrod, F, et al.
Neonatal recognition of familial dysautonomia.
J Pediatr 1987 Jun;110(6):946-8.

Summary Of Familial Dysautonomia Symptoms 

Familial dysautonomia affects the autonomic nervous system, the part of the nervous system that controls the "auto-pilot" functions of breathing, swallowing, heart rate changes, blood pressure, and temperature regulation. In other words, the part of the nervous system that manages all the essential functions so that you don't have to think about doing them. It also affects the sensory nervous system, the part of the nervous system that you use to feel pain and temperature. In addition to the main symptoms that make the criteria for the diagnosis, there are many other symptoms that have been seen with familial dysautonomia. Most of these are complications of the effect on the nervous system. The following is a list of possible symptoms; no patient will have all of these symptoms and many will experience only a few at a given time:


  • lack of overflow tears (dry eyes)
  • corneal wounds (with poor healing)
  • optic atrophy
  • strabismus 


  • lack of fungiform papilla on the tongue
  • small jaw size with overcrowding of teeth
  • early tooth loss


  • uncoordinated suck and swallow
  • episodes of cyclic vomiting
  • reflux (heartburn)
  • achalasia
  • motility problems (constipation, dumping syndrome)


  • episodes of erratic fast heart rate and high blood pressure
  • low blood pressure (hypotension)
  • dysrhythmias


  • Recurrent pneumonias due to aspiration
  • Inability to tolerate lower oxygen levels


  • dehydration with elevated blood urea nitrogen (BUN)
  • poor kidney blood flow
  • salt wasting
  • renal insufficiency or failure

Nervous system:

  • autonomic dysfunction
  • decreased ability to feel pain or temperature
  • hypotonia
  • decreased deep tendon reflexes
  • ataxia and apraxia
  • "dysautonomic crisis"
    (episodes of erratic blood pressure, heart rate, cyclical vomiting, gaseousness,
    temperature instability, excessive sweating and salivation, anorexia, and apparent discomfort)
  • seizures (due to breath-holding, febrile, and seizure disorders)
  • dizziness, passing out


  • scoliosis
  • kyphosis
  • exaggerated lordosis
  • neuropathic joints
  • inability to feel fractures


  • poor wound healing
  • blotching with eating, excitement, or sleeping
  • excessive sweating (especially on the head)


  • poor attention span
  • anxiety
  • depression
  • auditory processing problems
  • self-mutilation
  • separation anxiety


  • breech presentation at birth
  • low birth weight
  • variable and late decelerations during labor
  • temperature instability in the newborn period


  • delayed puberty
  • delayed gross motor and speech development

Lab Findings:

  • elevated BUN
  • elevated DOPA:DHPG ratio
  • anemia


  • breath-holding (at end of expiration, person arches and stiffens, eyes roll back in the head, often can turn blue especially around the lips, passes out)
  • poor weight gain
  • small stature

Dysautonomia Treatment and Evaluation Center


  1.    Sarwark JF and Kramer 
    A Pediatric Spinal Deformity.

    Curr Opin Ped 1998 Feb;10(1):82-6.
  2.    Groom, et al. 
    Optic Neuropathy in familial dysautonomia.

    J Neurophthalm 1997 Jun;17(2):101-2. 
  3.  Axelrod, et al. 
    Electrocardiographic measures and heart rate variability in patients with familial dysautonomia. 

    Cardiology 1997 Mar-Apr;88(2):133-40.
  4.    Axelrod FB 
    Familial dysautonomia: a 47-year perspective. How technology confirms clinical acumen. 

    J Pediatr 1998 Mar;132(3 Pt 2):S2-5.
  5.    Mass, et al. 
    A cephalometric evaluation of craniofacial morphology in familial dysautonomia.

    Cleft Palat Craniofac J 1998 Mar;35(2):120-6.
  6.    Kaplan, et al. 
    Aspects of spinal deformity in familial dysautonomia (Riley-Day syndrome).

    Eur Spine J 1997;6(1):33-8.
  7.    Axelrod FB 
    Familial Dysautonomia, 

    Manual of Comprehensive Care. 1997, Dysautonomia Foundation, Inc: New York.
  8.    Szold, et al.
      Laparoscopic-modified Nissen fundoplication in children with familial dysautonomia. 

    J Pediatr Surg 1996 Nov;31(11):1560-2.
  9.    Mass E and Gadoth N 
    Oro-dental self-mutilation in familial dysautonomia.
      J Oral Path Med 1994 Jul;23(6):273-6.
  10.    Axelrod, et al
    The effects of postural change and exercise on renal haemodynamics in familial dysautonomia. 
    Clin Auton Res 1993 Jun;3(3):195-200.
  11.    Leiberman, et al 
    Cesarean section by local anesthesia in patients with familial dysautonomia. 
    Am J Obstet Gynecol 1991 Jul;165(1):110-1.
  12.    Guidera, et al 
    Orthopaedic manifestations in congenitally insensate patients. 
    J Ped Orthoped 1990 Jul-Aug;10(4):514-21.
  13.    Okada F 
    Psychiatric aspects of acute pandysautonomia.
    Eur Arch Psychiatry Clin Neurosci 1990;240(2):134-5.
  14.     Axelrod, et al 
    Neonatal recognition of familial dysautonomia. 
    J Pediatr 1987 Jun;110(6):946-8.
  15.    Gwathmey, et al.
    Clinical manifestations of congenital insensitivity of the hand and classification of syndromes. 
    J Hand Surg (Am) 1984 Nov;9(6):863-9.
  16.    Gadoth, et al.
    Sleep structure and nocturnal disordered breathing in familial dysautonomia. 
    J Neurol Sci 1983 Jul;60(1):117-25.
  17.    Ganz, et al. 
    Physical therapy management of familial dysautonomia. 
    Phys Ther 1983 Jul;63(7):1121-4.
  18.    Gadoth, et al.
    Presence of fungiform papillae in classic dysautonomia. 
    J Hopkins Med J 1982 Dec;151(6):298-301.
  19.    Clayson, et al 
    Personality development and familial dysautonomia.
    Pediatrics 1980 Feb;65(2):269-74.
  20.    Welton, et al.
    Intellectual development and familial dysautonomia. 
    Pediatrics 1979 May;63(5):708-12.

Genetics & FD

Familial Dysautonomia is a genetic disorder that affects primarily Ashkenazi Jews. It is an autosomal recessive disorder which means that every individual that is affected has inherited one copy of the genetic mutation from each of his parents. People who have only one copy of the mutation are known as carriers and since they are unaffected, are not aware they have the mutation until they have a child with familial dysautonomia.

Chromosomes are the blueprint for how a body's cells develop and function. Every person has 23 pairs of chromosomes. One chromosome of each pair is inherited from one's mother and the other chromosome is inherited from one's father. Chromosomes are made up of strands of a molecular substance called DNA. Sections of the DNA strands which make proteins are called genes. It is our genes that determine how certain traits will be expressed and tell our body's cells how to function. When there is an error within a portion of a gene's DNA, it is called a mutation and the gene does not function the way it should.

Chromosomes have many different functions. The part of the chromosome that makes up the genes are only a small portion of the total DNA in the chromosomes. These gene sections are called exons. Between the exons are sections of DNA called introns, enhancers, 3'-UTR, promoter, and other regions, which tell the chromosome important things like when to turn a gene on and off. The intron regions, previously thought to be "junk" DNA, are now believed to hold information like how an individual reacts to certain drugs.

Familial Dysautonomia mutation:
Familial dysautonomia is caused by a mutation in a protein called IKAP. The function of the IKAP protein is not well understood at present. There are two known mutations. The major mutation is found in 99.5% of all patients and results in the deletion of a coding region of this protein. The second and minor mutation results in the substitution of an amino acid in an important regulatory region of the protein. The presence of one major mutation that is found in so many affected individuals and carriers is due to the founder effect. This is called founder effect because it is believed that one person (the founder) had a spontaneous mutation on one of his/her chromosomes. All carriers (and therefore all affected individuals) are descendents of this founder and as such share the same portion of DNA.

Estimating A Family Member's Risk for Being a Familial Dysautonomia Carrier

We know that the parents of a child with familial dysautonomia are each carriers (one normal chromosome and one with the DYS mutation). The child with familial dysautonomia has inherited the chromosome containing the DYS mutation from each parent. In any future pregnancy, there are four possible outcomes: inheriting mom's normal and dad's DYS, inheriting mom's DYS and dad's normal, inheriting normal chromosomes from both, or inheriting the DYS mutation from both. Therefore the chance of having any one of the above possibilities is one in four (25%). Since we know that unaffected siblings have not inheritied the DYS mutation from both parents (or else they would have FD), they have only three possible chromosome combinations (DYS from mom, normal dad or normal mom, DYS from dad). Carrier status is seen with two of these possibilities. Therefore, siblings of individuals with FD have a two in three chance of being carriers (67%). The following table states the risk of being an FD carrier for family members of different levels of relation to an individual with FD.

Brother or Sister 67% (2 in 3)
Parents 100% (both are carriers)
Uncle, Aunt, Grandparents 52% (approx. 1 in 2)
First Cousin* 28% (approx. 1 in 4)
First Cousin's Child, Parent's First Cousin 17% (approx. 1 in 6)
Second Cousin** 10% (approx. 1 in 10)
Second Cousin's Child 7% (approx. 1 in 6)
General Population Risk 3% (1 in 30)
*uncle or aunt's child 
**mother or father's first cousin's child 

This table assumes that all relatives are Ashkenazi Jews and therefore includes the baseline 1 in 30 risk from each parent unrelated to the affected individual. If non-Ashkenazi Jews are included in your family tree, then the risk would be less.


  1. Blumenfeld A, et al.
    Precise Genetic Mapping and Haplotype Analysis of the Familial Dysautonomia Gene on Human Chromosome 9q31. Am J Hum Gen 1999 Apr;64(4):1110-1118.

  2. Eng, CM, et al.
    Prenatal diagnosis of familial dysautonomia by analysis of linked CA-repeat polymorphisms on chromosome 9q31-q33. Am J Med Genet 1995 Nov 20;59(3):349-55.

  3. Oddoux, C, et al.
    Prenatal diagnostic testing for familial dysautonomia using linked genetic markers.
    Prenat Diagn 1995 Sep;15(9):817-26.

  4. Blumenfeld, A, et al.
    Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis. Nat Genet 1993 Jun;4(2):160-4.