Genetic Counseling for Families of Patients With Fragile X SyndromeGenetic Counseling for Families of Patients With Fragile X Syndrome

To the Editor: Dr Jacquemont and colleagues¹ reported that male carriers of premutation alleles of the FMR1 gene are at risk of developing fragile X–associated tremor/ataxia syndrome (FXTAS). We are concerned that the authors did not discuss genetic counseling in the process of testing these individuals, which raises several ethical issues. First, when a male carrier passes on his deleterious allele (on the X chromosome) to his daughters, they become obligate carriers of the premutation. By identifying a man with FXTAS, his daughters are necessarily identified as FMR1 premutation carriers. As the authors stated, not only is the CGG repeat prone to expansion when passed through the female (thus the risk of fragile X syndrome in her offspring), but approximately 20% of women with FMR1 premutations will also experience premature ovarian failure. Although this may be very valuable family planning information for those daughters, we are troubled with the concept of diagnosing female offspring with a deleterious allele without considering these implications or potentially without their knowledge.

Second, when older men who exhibit parkinsonism-like symptoms are identified as FMR1 premutation carriers, it is not clear how this information would change medical management. Additional costly medical work-up could be avoided when the diagnosis is made, but this medical benefit must be considered in light of the consequences for the patient's daughters.