Familial Dysautonomia Research Paper

Familial dysautonomia (FD), also called Riley Day Syndrome and hereditary and sensory autonomic neuropathy type 3 (HSAN3), is an inherited disorder that affects the development and survival of some sensory and autonomic neurons.4,5 It is almost exclusively present in Ashkenazi Jews. About 1 out of 32 Ashkenazi Jews are carriers. The disease frequency is 1 out of 3700 for Ashkenazi Jews.5 Familial dysautonomia is exceedingly rare in the non Ashkenazi Jewish population.

The symptoms of familial dysautonomia may be present at birth.4,5 However, in general, the symptoms are not typically apparent until infancy. The earliest symptoms are difficulties in feeding and swallowing, which may result in aspiration pneumonia (infection that forms the presence

About 1/3 of students diagnosed with familial dysautonomia have learning disabilities, including short attention spans. As the children grow older, their symptoms worsen. They have more difficulty walking. They may have lung damage from repeated lung infections. Their vision becomes worse, as their optic nerves

However, the symptoms may vary greatly among individuals. Still, there are five requirements that almost all patients with FD meet.4,5 Patients typically are of Ashkenazi Jewish heritage, do not have fungiform papillae on the tongue, cannot produce tears, have diminished patellar reflexes, and do not demonstrate an axonal flare after histamine is injected (normal patients develop a small red bump, but FD patients do not).4,5 If these symptoms are present, the disease can be diagnosed via a DNA test for known mutations on the IKBKAP gene.

Familial dysautonomia is an autosomal recessive disorder, which is a result of mutations in the IKB kinase-complex-associated protein (IKBKAP) gene, located on chromosome 9(q31).1,2 Over 99% patients with FD have a homozygous point mutation (TC) at the donor splice site on intron 20.2,4 This results in alternative splicing, which excises exon 20. This creates a frameshift mutation that results in premature termination codon and a truncated IKAP protein. In 4 individuals, heterozygous for FD, an additional missense mutation was found at exon 19, which results in the phosphorylation of the IKAP