Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey

Parents enrolling in a national survey of families of children with fragile X (FX) reported whether each of their children had been diagnosed or treated for developmental delay or eight conditions frequently associated with FX: attention problems, hyperactivity, aggressiveness, self-injury, autism, seizures, anxiety, or depression. This article reports results for 976 full mutation males, 259 full mutation females, 57 premutation males, and 199 premutation females. Co-occurring conditions were frequently reported for all FMR1 gene variations. The number of co-occurring conditions experienced was strongly associated with parent reports of their child's ability to learn, adaptability, and quality of life. Most individuals with the full mutation experienced multiple co-occurring conditions, with a modal number of 4 for males and 2 for females. Most (>80%) full mutation males and females had been diagnosed or treated for attention problems. Premutation males, when compared with a matched group of non-FX males, were more likely to have been diagnosed or treated for developmental delay, attention problems, aggression, seizures, autism, and anxiety. Premutation females were more likely to have been diagnosed or treated for attention problems, anxiety, depression, and developmental delay. Clusters of conditions were identified, seeming to occur in an additive fashion. Self-injury, autism, and seizures rarely occurred in isolation, but were more likely in individuals who also had problems with attention, anxiety, and hyperactivity. The findings provide a reference point for future studies on the prevalence and nature of co-occurring conditions in FX; suggest the possibility that certain conditions cluster together; provide evidence that male and female carriers experience elevated rates of co-occurring conditions compared with matched groups of non-carrier children; and emphasize the importance of including an assessment of co-occurring conditions in any clinical evaluation of individuals with abnormal variation in the FMR1 gene

Bailey, D., Raspa, M., Olmsted, M., & Holiday, D. (2008). Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey. American Journal of Medical Genetics. Part A, 146A(16), 2060-2069.