Family involvement in Fragile X: Testing, and counseling guidelines
Purpose: Molecular advances in understanding the transcription and translation of the FMR1 gene have lead to an appreciation of clinical problems experienced by carriers of the FMR1 premutation (55 to 200 CGG repeats) in addition to those with the full mutation (>200 repeats). Clinical involvement in a subgroup of premutation carriers includes ADHD and social deficits often on the autism spectrum in young males, whereas older male and female carriers (>50 years) can develop the fragile X-associated tremor/ataxia syndrome (FXTAS)or premature ovarian failure. The purpose of our project was to develop consenses regarding FMR1 testing guidelines and subsequent genetic counseling and cascade testing recommendations.
Methods: Focus groups were carried out with a core group of genetic counselors and neurologists, psychiatrists, psychologists,pediatricians, obstetricians, reproductive medicine specialists, molecular biologists, family practice professionals in addition to researchers in the fragile X filed and professionals from the Centers of Disease Control (CDC)and family members.
Results: Consensus was reached regarding individuals to be tested for the FMR1 mutation including all children and adults with mental retardation or autism or autism spectrum disorders with unknown etiology, adults with onset of intention tremor or ataxia after age 50 years,adults with neurological problems and a family history of fragile X, women with premature ovarian failure of unknown etiology, Atypical Parkinson's Disease (Parkinson's plus) in individuals over age 50, individuals with the middle cerebellar peduncle sign on MRI, children with learning disabilities or emotional problems and physical features of fragile X, family history of infertility/premature menopause, ataxia, developmental disabilities, or autism along with neurological symptoms in the presenting patient, individuals with a positive family history of the FMR1 mutation.
Conclusions: Testing for the FMR1 mutation involves a larger group of individuals that previously tested because of newly discovered phenotypes in premutation carriers. New guidelines will be presented in detailed along with genetic counseling and cascade testing recommendations.