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Familial dysautonomia (FD) affects the development and survival of sensory, sympathetic, and parasympathetic neurons. It is a debilitating disease present from birth. Neuronal degeneration progresses throughout life. Affected individuals have gastrointestinal dysfunction, vomiting crises, recurrent pneumonia, altered sensitivity to pain and temperature perception, and cardiovascular instability. About 40% of individuals have autonomic crises. Hypotonia contributes to delay in acquisition of motor milestones. Older individuals often have a broad-based and ataxic gait that deteriorates over time. Life expectancy is decreased.
The diagnosis of FD is established by molecular genetic testing of IKBKAP. Such testing is available clinically. Two mutations account for more than 99% of mutant alleles in individuals with FD of Ashkenazi Jewish descent. The major founder mutation c.2204+6T>C (formerly IVS20+6T>C) is responsible for virtually all occurrences of FD among the Ashkenazim.
Familial dysautonomia is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the chance of his/her being a carrier is 2/3. Carrier testing and prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutations in the family are known.