Genetic Testing

FD is transmitted in a recessive fashion.

• For a child to be affected, he or she must inherit two copies of the FD gene.
• All parents of children with FD are carriers of the recessive gene that transmits the disease.
• A parent or carrier has no symptoms or warning signs of being a carrier of the FD gene.
• If two carriers have a child, there is a 25% chance with each pregnancy that the recessive genes will pair and result in a child being affected with FD.

The FD gene has been localized to the long arm of chromosome 9 (9q31) and the gene has been identified as IKBKAP. Three mutations in the FD gene have been described. The most common mutation is in intron 20; >99% of FD individuals are homozygous for this mutation that results in skipping of exon 20. The degree of skipping is tissue specific. Thus, the gene product, IKAP, is not expressed at all in the brain but can be expressed to some degree in other body areas. The other mutations are very rare and to cause FD, they have always been paired with the "common" mutation.

Prenatal diagnosis and carrier testing is now available for the general population.

How is testing performed?

Genetic testing is performed on a small sample of blood from the interested individual. The DNA is examined with a special probe designed to detect the known specific mutations. The reliability of the test is greater than 99%.

Who should be tested?

• Any individual with Ashkenazi Jewish (Eastern European) origin has a 1 in 30 risk of being a carrier and should consider screening.
• Any individual who has a family history of FD has an increased risk of being a carrier and should consider a screening test.
• If your partner is a carrier, then you should be tested.
  

Prenatal diagnosis

If both members of a couple are shown to be carriers by genetic testing, prenatal diagnosis by amniocentesis (14-17 weeks) or chorionic villus sampling (10-11 weeks) is possible.

Where is testing performed?

Testing is performed only after the interested person has received genetic counseling to clarify the benefits and limitations. The Dysautonomia Foundation's designated genetic counseling center is at NYU School of Medicine. Israelis may receive genetic counseling at Haddassah Medical Center.

Genetic tests are performed only with an individual's consent. Other genetic tests will not be performed in the absence of consent. However, from a single blood sample it is possible to test for other conditions that also affect Ashkenazi Jewish children. These include Tay-Sachs disease, Canavan disease, cystic fibrosis, Gaucher disease, Bloom syndrome, Fanconi anemia A, and Niemann-Pick disease.