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.
Pain insensitivity - Insensitivity or indifference to painful stimuli may lead to frequent/progressive self-mutilation, burns, and ulcers. There may be self-mutilation of the tongue (especially in toddlers during teething), lips, and cheeks, or loss of teeth. Compulsive oral biting may result in ulcers, or tumour-like masses (Riga-Fede disease). Progression
Familial dysautonomia presents with progressive age-specific symptoms. Though usually not diagnosed until several years of age, generalised signs of FD are present in during the newborn period >80% of those affected.Dysmorpnic facial features are not directly inherent to the disorder, however, facial asymmetry and a straightened mouth eventually develop due to abnormal tone and molding of facial bones. Perinatal
A very high incidence of breech presentation has been noted among infants with FD. A lower birth weight as compared to siblings, premature birth, and intrauterine growth restriction have also been noted. Neonatal
During the neonatal period, there may be hypotonia, respiratory insufficiency, poor feeding with difficulty swallowing and aspiration, developmental delay, short stature, scoliosis, and corneal disease. Infancy
Issues related to the disorder first appear during infancy. Early manifestations include hypotonia, feeding difficulty (impaired swallowing and suckling), poor growth, absence of tears, frequent lung infections, and poor body temperature control (infants may display cold hands and feet). Developmental milestones (e.g.