Genetic Counseling and Testing for FMR1 Gene Mutations: Practice Guidelines of the National Society of Genetic Counselors

Abstract

Fragile X syndrome (FXS) is one of several clinical disorders associated with mutations in the X-linked Fragile X Mental Retardation-1 (FMR1) gene. With evolving knowledge about the phenotypic consequences of FMR1 transcription and translation, sharp clinical distinctions between pre- and full mutations have become more fluid. The complexity of the issues surrounding genetic testing and management of FMR1-associated disorders has increased; and several aspects of genetic counseling for FMR1 mutations remain challenging, including risk assessment for intermediate alleles and the widely variable clinical prognosis for females with full mutations. FMR1 mutation testing is increasingly being offered to women without known risk factors, and newborn screening for FXS is underway in research-based pilot studies. Each diagnosis of an FMR1 mutation has far-reaching clinical and reproductive implications for the extended family. The interest in large-scale population screening is likely to increase due to patient demand and awareness, and as targeted pharmaceutical treatments for FXS become available over the next decade. Given these developments and the likelihood of more widespread screening, genetic counselors across a variety of healthcare settings will increasingly be called upon to address complex diagnostic, psychosocial, and management issues related to FMR1 gene mutations. The following guidelines are intended to assist genetic counselors in providing accurate risk assessment and appropriate educational and supportive counseling for individuals with positive test results and families affected by FMR1-associated disorders.