Familial dysautonomia (FD), also known as Riley-Day Syndrome, is a rare, progressive, recessive genetic disorder of the autonomic nervous system that affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system. FD results in variable symptoms, including insensitivity to pain, inability to produce tears, poor growth and labile blood pressure (episodic hypertension and postural hypotension). People with FD have frequent vomiting crises, pneumonia, problems with speech and movement, difficulty swallowing, inappropriate perception of heat, pain and taste as well as unstable blood pressure and gastrointestinal dysmotility. Originally reported by Drs. Conrad Milton Riley and Richard Lawrence Day in 1949, FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies (HSAN). All HSAN are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.
There have been three mutations in IKBKAP identified in individuals with FD. The most common FD-causing mutation occurs in intron 20 of the donor gene. Conversion of T→C in intron 20 of the donor gene resulted in shift splicing that generates an IKAP transcript lacking exon 20. Translation of this mRNA results in a truncated protein lacking all of the amino acids encoded by exons 20–37. Another less common mutation is a G→C conversion resulting in one amino acid mutation in 696, where Proline substitutes normal Arginine. The decreased amount of functional IKAP protein in cells causes familial dysautonomia. Diagnosis
Clinical diagnosis
A clinical diagnosis of FD is supported by a constellation of criteria:
No fungiform papillae on the tongue
Decreased deep tendon reflexes
Lack of an axon flare following intradermal histamine
No overflow tears with emotional crying

Genetic testing
Genetic testing is performed on a small sample of blood from the tested individual. The DNA is examined with a designed probe specific to the known mutations. The accuracy of the test is above 99%. Dr. Anat Blumenfeld of the Hadassah Medical center in Jerusalem identified chromosome number 9 as the responsible chromosome. Prenatal testing
Familial dysautonomia is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. If both parents are shown to be carriers by genetic testing, there is a 25% chance that the child will have FD. For pregnancies at increased risk for FD, preimplantation genetic diagnosis or prenatal diagnosis by amniocentesis (at 15–17 weeks) or chorionic villus sampling (at 10–14 weeks) is possible.