Genetic Counseling and Testing for FMR1 Gene Mutations

Centers offering population screening should ensure that they have the resources available to provide pre‐ and post‐test genetic counseling that supports the psychosocial and clinical needs of the patient and family. In light of widespread FMR1 testing among women without known risk factors, genetic counselors should anticipate seeing patients who did not receive any pre‐test information, have no prior knowledge of FMR1‐associated disorders, and are unprepared to learn that they have an FMR1 mutation.

Although many genetic counselors are familiar with FXS, fewer have experience with FXTAS and FXPOI. As such, they may underestimate the scope of clinical inquiry needed for risk assessment in families with FMR1 mutations. Taking a pedigree in these families requires attention to a diverse constellation of developmental, neurodegenerative, and reproductive symptoms that vary widely in age of onset and severity across multiple generations. Specific family history queries designed to identify individuals with the full spectrum of FMR1 gene mutations are listed in Table 7. Given the subjective nature of behavioral and cognitive symptoms, psychiatric and educational records should be obtained whenever possible to confirm a reported history of developmental issues.

The diagnosis of FMR1‐associated disorders can have far‐reaching genetic and emotional implications for extended family members. When an FMR1 mutation is identified in a family, genetic counselors should assist patients in developing strategies to inform relatives.

Parents should be encouraged to explore open and meaningful discussion with their children about FMR1‐associated disorders and genetic risk. Genetic counselors should work toward helping parents develop a positive, resilient communication style which may aid in the long‐term adaptation of children to FMR1‐related risk.

Psychiatric issues, as well as cognitive decline, are common among patients with FXTAS. They may experience confusion and emotional reactions to learning the genetic nature of their condition and its implications for their children and other relatives. With the patient's consent, it may be important to involve other family members and caregivers in these discussions so that genetic and management information is accurately communicated.

Patients who have normal laboratory results should be counseled that FMR1 testing does not rule out other genetic conditions or determine the cause of undiagnosed developmental disabilities, infertility, or neurodegenerative disorders in other family members.