Chicago Center for Jewish Genetics Disorders - Ashkenazi Disorders: Familial Dysautonomia

Ashkenazi Disorders: Mendelian

Gene: The gene causing familial dysautonomia is IKBKAP, which is located at 9q31. This encodes a protein involved in the development and maintenance of the sensory and autonomic nervous systems.

Mutations and testing: Two mutations have been seen in all of the cases of familial dysautonomia tested for at this time. The major mutation is IVS2+6T-C and it accounts for more than 99.5% of mutant alleles seen thus far. With this mutation varying levels of wild-type message are expressed in a tissue-specific manner, with the deleted message seen only in the brain. In other words, the major mutation doesn't cause complete inactivation of the IKBKAP protein in all tissues of the body, only in the brain. The other mutation, the so-called "minor mutation," is R696P. As of 2001, only 4 patients have been reported to have the minor mutation. Each of these patients is a compound heterozygote for the major mutation and the minor mutation. No homozygotes for the minor mutation have been identified.

Traits: Familial dysautonomia (FD) is associated with poor development and survival, and progressive degeneration of the sensory and autonomic nervous system. Marked and progressive depletion of unmyelinated sensory and autonomic neurons has been seen in patients with FD, and is believed to start early in fetal life. FD is clinically characterized by 5 main characteristics: absence of fungiform papillae on tongue, absence of flare after injection of intradermal histamine, decreased or absent deep-tendon reflexes, absence of overflow emotional tears (alacrima), and Ashkenazi Jewish heritage. Other common characteristics include: gastrointestinal dysfunction, such as reflux and vomiting; abnormal respiratory responses to low levels of oxygen and high levels of carbon dioxide in the blood; scoliosis; poor coordination; sensory impairment with regard to pain, heat, and cold; inappropriate sweating and lack of temperature control; and postural hypotension. At this time only 50% of patients live to 30 years of age due to cardiovascular, pulmonary, and gastrointestinal problems.

Treatment: Treatment is supportive only. Artificial tears can be helpful, as well as medications to help control abnormal blood pressure, nausea, and vomiting.

Familial Dysautonomia from Geneclinics.org
http://www.genetests.org/profiles/fd

Reviewed by Dr. Joel Charrow, Children's Memorial Hospital.
1/03

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This page last updated on January 10, 2003.