Adults Living With Fragile X Syndrome
Fragile X syndrome (FXS) is a rare genetic disorder characterized by developmental disabilities, learning and cognitive impairments, behavioral challenges, and various physical features. FXS is the known leading cause of inherited intellectual disability and the leading single-gene cause of Autism Spectrum Disorder (ASD). FXS is caused by the full mutation of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene located on the X chromosome. Fragile X gets its name from a segment of the X chromosome that appears “fragile” or “broken” under a microscope.1
The signs and symptoms of Fragile X syndrome and their challenges can vary widely from person to person. Adults with FXS may face unique challenges, such as problems with memory, abstract thinking, problem-solving, and planning.2 Adult females with FXS frequently exhibit social avoidance, mood disorders, attention deficits, and learning disabilities.3
Anxiety and depression are widespread in individuals with FXS, as are social and behavioral issues, developmental delays, and autistic behaviors. People with FXS are also more likely to develop certain health concerns, such as ear infections, difficulty sleeping, seizures, and gastrointestinal issues, such as diarrhea and gastric reflux.2
Individuals with FXS often take considerably longer to reach developmental milestones and struggle to master the adaptive skills necessary for everyday life.2 Although the symptoms of FXS do not worsen over time, the way in which the disorder manifests in a person may vary throughout different stages of their lives, including, as discussed below, adulthood.
Intellectual Disability in Adults With FXS
FXS affects both males and females; however, females may experience milder symptoms than males. Males with FXS are more likely than females to be diagnosed with an intellectual or developmental disability. Males usually have mild to severe intellectual disabilities, whereas only around one-third of affected females have an intellectual disability.4 This gender-based disparity in intellectual functioning is because females have two X chromosomes (of which only one is impaired with FXS), whereas males have just one X chromosome.4 Given this milder presentation, some adult females with the full FMR1 gene mutation may lead more typical adult lives, including living independently, pursuing higher education, working full-time, having friends, and engaging in various recreational activities.4 Adult males with FXS, on the other hand, are more likely to have limited independence regarding their employment, residence, ability to perform everyday activities, form friendships, and enjoy leisure activities.4
The most common jobs for adult males with FXS are production, assembly, cleaning, maintenance, and food preparation or service jobs. In comparison, the most common jobs for females with FXS are education, training, library work, cashier, clerical or retail work, and office work. However, only two out of every ten males are employed full-time, compared to nearly half of the females with FXS. The most common leisure activities for adults with FXS are watching TV, listening to music, and playing video games.4
Functional Challenges in Adults With FXS
Functional skills, such as eating, dressing, toileting, and communicating, are often impaired in adults with FXS. These impairments in daily living skills have been shown repeatedly to have a strong correlation with various outcomes for adults with intellectual disabilities, including employment success and the ability to form friendships.4
Well-rounded interpersonal skills are crucial for adult life. However, since Fragile X syndrome is associated with deficits in social communication and interaction, increased social anxiety, and autistic mannerisms (such as poor social awareness and restricted and repetitive behavior), the degree to which adults with FXS can interact with others may correspond to their independence in various dimensions of adult life.4
Co-occurring Mental Health Conditions in Adults With FXS
Individuals with FXS have an increased risk of co-occurring mental health conditions.4
- Depression and anxiety have reportedly been found to occur in about one-half to more than two-thirds of males and females with FXS (between the ages of four and 59).4
- Attention problems and hyperactivity have also been reported in about 80% of children and adults with FXS.4
- Furthermore, aggression and self-injurious behavior occur in adults but are more common in males than females, with more than 40% of males being diagnosed with or treated for problems with aggression (43%) and self-injury (47%) as compared to 13% and 17% respectively in females.4
The degree to which these co-occurring mental health problems affect the level of independence in adult life for females and males requires further study.4 However, preliminary studies utilizing heterogeneous samples of adults with an intellectual disability or other genetic disorders associated with intellectual disability have indicated that co-occurring mental health conditions are often important predictors of adult outcomes, such as unemployment and less independent residential placement.4
Hospitals, residential treatment centers, and mental health facilities are among potential residential placement settings for adults with FXS. Less independent residential placement settings for adults with FXS and co-occurring mental health disorders (requiring considerable assistance in day-to-day activities) include group homes or co-residing with parents.4
Level of Independence in Adults With FXS
Adults with fragile X syndrome have varying levels of independence. Four in ten females and one in ten males with FXS are able to reach a high or very high level of independence in adult life, according to surveys,5 while others may have considerably more limited independence in these areas and others, such as housing, employment, and daily living activities.4 In time, individuals with FXS may be able to do more on their own and have fewer behavioral issues, but this trend may level off or even reverse by the time they hit their 30s.6
Adult Premutation Carriers
Individuals with FXS have a full mutation of the FMR1 gene (the CGG region is repeated more than 200 times). However, individuals with 55-200 CGG repeats in their FMR1 gene are known as Fragile X premutation carriers. Premutation carriers do not have Fragile X syndrome but may have or later develop other Fragile X-associated disorders, such as Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) or Fragile X-Associated Primary Ovarian Insufficiency (FXPOI).9
- Fragile X-Associated Tremor/Ataxia Syndrome – Characterized by unsteadiness (ataxia), memory problems, and intention tremors, FXTAS is an adult-onset neurodegenerative disorder usually affecting males over 50 years of age. Females account for a rather small proportion of the FXTAS population and tend to have less severe symptoms. Among premutation carriers, about 40% of males over 50 and 8-16% of females over 40 develop FXTAS. The condition progresses at varying levels in different individuals. It may be one of the most common adult-onset, single-gene neurological disorders similar in prevalence to other neurodegenerative disorders such as Lou Gehrig’s disease (ALS).10
- Fragile X-Associated Primary Ovarian Insufficiency – Approximately 10-30% of female premutation carriers develop FXPOI. The condition encompasses a range of clinical symptoms of ovarian dysfunction, including irregular menstrual cycles, increased follicle-stimulating hormone, fertility problems, and menopause before the age of 40. For some premutation carriers, menopause can begin in their early 20s. Although the mechanism underlying the development of FXPOI remains largely unknown, there appears to be a non-linear relationship between the severity of FXPOI and CGG repeats, with the greatest risk and earlier onset reported among those with CGG repeat in the 80-100 range. Approximately 5% of POI cases are related to an FMR1 expansion.9
It’s important to remember that not everyone with an FMR1 premutation goes on to develop a Fragile X-associated condition and that how someone experiences a condition might vary widely. Researchers are still studying to understand why this is the case.10
How Is Fragile X Syndrome Inherited?
Since the FMR1 gene is located on the X chromosome, both males (XY) and females (XX) can pass on the mutated gene to their children. However, a father with a mutated FMR1 gene will only pass it on to his daughters. To his sons, he will pass on the Y chromosome, which does not contain the mutated gene. In contrast, a mother with a mutated FMR1 gene has a 50/50 chance of passing it on to her children, sons, and daughters.11
It is worth noting that a father can only pass on the premutation to his daughters, even if he has a full mutation. The exact reason for this remains an area of focused research.11
Where FXS or a Fragile X premutation is suspected, consultation with a health care provider is recommended. During that consultation, testing options such as prenatal testing, newborn screening, and other forms of genetic testing may be discussed. Genetic counselors, medical geneticists, health care providers, or a Fragile X clinic available throughout the United States may be consulted for specific information about genetic testing and results.
- Cleveland Clinic. Fragile X Syndrome. Retrieved Nov 30, 2022, from https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention. Fragile X syndrome: Learning what families need, one person at a time. Retrieved Nov 30, 2022, from https://www.cdc.gov/ncbddd/fxs/features/learning-what-families-need.html
- National Fragile X Foundation, The Unique Challenges for Females with Fragile X Syndrome. Retrieved Jan 23, 2023, from https://fragilex.org/fxs/uniqueness-females-fragile-x-syndrome/
- Hartley SL, Seltzer MM, Raspa M, Olmstead M, Bishop E, Bailey DB. Exploring the adult life of men and women with fragile X syndrome: results from a national survey. Am J Intellect Dev Disabil. 2011 Jan;116(1):16-35. Doi: 10.1352/1944-7558-116.1.16. PMID: 21291308; PMCID: PMC3238098.
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention. Data and Statistics on Fragile X Syndrome. Retrieved Jan 23, 2023, from https://www.cdc.gov/ncbddd/fxs/data.html
- Fragile X News Today. Independence of Fragile X Patients Increases Until Their 30s, Then Starts to Decline, Study Says. Retrieved Jan 23, 2023, from https://fragilexnewstoday.com/news/independence-of-fragile-x-patients-increases-until-their-30s-then-starts-to-decline-study-says/#:~:text=People%20with%20fragile%20X%20syndrome,their%2030s%2C%20a%20study%20suggests.
- Centers for Disease Control and Prevention, How Fragile X Syndrome Is Inherited. Retrieved Jan 23, 2023, from https://www.cdc.gov/ncbddd/fxs/inherited.html
- National Fragile X Foundation, Fragile X-Associated Tremor/Ataxia Syndrome / FXTAS. Retrieved Jan 23, 2023, from https://fragilex.org/understanding-fragile-x/tremor-ataxia-syndrome-fxtas/
- Birch RC, Cohen J, Trollor JN. Fragile X-associated disorders: Don’t miss them. Aust Fam Physician. 2017;46(7):487-491.women
- Fragile X Association of Australia, Fragile X Premutation Carriers. Retrieved Jan 23, 2023 from https://www.fragilex.org.au/understanding-fragile-x/fragile-x-premutation-carriers/
- National Institute of Child Health and Human Development, National Institutes of Health. Other Fragile X Syndrome FAQs. Retrieved Jan 23, 2023, from https://www.nichd.nih.gov/health/topics/fragilex/more_information/faqs#:~:text=The%20gene%20for%20Fragile%20X,on%20only%20to%20his%20daughters.