Respiratory aspects of Riley-Day Syndrome: Familial Dysautonomia

Abstract

Familial Dysautonomia (FD), or Riley-Day Syndrome after the two doctors who first described it in 1949, is an autosomal recessive genetic disease. It is also known as Hereditary Sensory and Autonomic Neuropathy III (HSAN III). Almost all FD patients are of eastern European Ashkenazi Jewish descent. Among this population, the incidence rate is 1:3703 of live births, the carrier rate is 1/32 and 1/18 in Jews of Polish origin. The gene for FD was discovered in 2001 and prenatal diagnosis is now available. Up to now 3 mutations were identified. The major homozygote mutation is responsible for >99.5% of the FD cases. In a few of cases, the mutation is compound heterozygote including the major mutation and a minor mutation. The third mutation was discovered in only one individual, and originates from a mother who is not an Ashkenazi Jew. The FD gene is called IKBKAP (Inhibitor of Kappa light polypeptide gene enhancer in B cells Kinase complex Associated Protein) and it was found to be on chromosome 9q31. It includes 37 axons and encodes the protein IKAP (I-kB Kinase Associated Protein) which is composed of 1332 amino acids. The role and the mechanisms by which the mutated protein causes FD have not yet been fully determined. Possibly IKAP is involved in the reaction of mammals to stress. In the major mutation there is a deletion in axon 19 of the mRNA IKBKAP. Both the normal protein and the shortened protein are found in FD patients, with the ratio