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.
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.
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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:
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.
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