Independence of Fragile X Patients Increases Until Their 30s, Then Starts to Decline, Study Says

People with fragile X syndrome experience greater independence in daily activities and less severe behavioral problems over time, a trend that stabilizes or reverses when they reach their 30s, a study suggests.

Researchers found that higher levels of autism spectrum disorder (ASD) symptoms were linked to lower independence and more behavioral problems as well, with patients also tending to gain weight and have more health conditions as they age.

These findings support the need for continuous and comprehensive treatment throughout the lifespan of fragile X patients.

The study, “Trajectories of Change in the Behavioral and Health Phenotype of Adolescents and Adults with Fragile X Syndrome and Intellectual Disability: Longitudinal Trends Over a Decade,” was published in the Journal of Autism and Developmental Disorders.

Fragile X is caused by a mutation in the FMR1 gene, the most common single gene known to cause inherited intellectual disability and autism.

Besides intellectual disability and ASD symptoms, people with fragile X often show impaired functional skills and behavioral problems, which have been reported as the most significant source of stress for caregivers and patients. In addition, patients can often become overweight with poor overall health.

While several studies have described fragile X symptoms during adolescence and adulthood, there is still limited data on the lifelong trajectory of the disease and its associated manifestations.

In the new study, researchers at the University of Wisconsin-Madison Waisman Center investigated the behavior and health trajectories of adolescents and adults with fragile X over nearly a decade, as well as the impact of gender and ASD symptoms on these trajectories.

The team analyzed the clinical data of 125 fragile X patients at four time points from 2008 to 2017.

All of the patients had intellectual disability, including 24.2% with ASD. Their mean age at the beginning of the study was 20.2 (range 12–48.9 years), and most were male (85.1%).

The vast majority (90.3%) of patients lived with their mothers, who were the main respondents for the study — through self-administered questionnaires and telephone interviews.

Behavior data included measures of independence in daily living — assessed through the Waisman Activities of Daily Living scale (W-ADL) — and behavioral problems, assessed by a specific subscale of the Scales of Independent Behavior-Revised.

Health data consisted of body mass index (BMI) and a number of health conditions (from a list of 36 pre-selected conditions). ASD symptoms were measured only at the beginning of the study using the Social Communication Scale.

At the end of the study period, 65.0% of the patients were in their 20s, 30.1% in their 30s, and 4.9% in their 40s.

Results showed that patients’ mean W-ADL scores were about 23 (on a scale with 34 indicating complete independence) at each time point. The proportion of patients with clinically significant behavioral problems was 52.4% at the beginning and 27.8% at the end of the study.

Overall, being independent in daily activities and experiencing behavioral problems appeared to stabilize or even reverse in people with fragile X syndrome after they reach their 30s. However, the data also suggested a decline in independence and an increase in behavioral problems in the oldest patients.

“Although independence in daily living skills increased during adolescence and early adulthood, by the early 30s and beyond there was a plateau or a decline in independence,” the researchers said.

The team noted that despite less-severe behavior problems over time, nearly one-third of patients still had clinically significant behavior problems at the last follow-up.

Mean BMI values increased over time, and the proportion of patients classified as overweight increased from 22.6% at study’s start to 32.2% at the last follow-up. The mean number of health conditions at each time point was less than one. Trajectories indicated linear increases in BMI and the number of health conditions over time.

More ASD symptoms at the beginning of the study were significantly associated with lower independence levels in daily tasks and higher levels of behavioral problems.

Gender did not significantly predict any of the evaluated trajectories. Since women were previously reported to have less severe disease, the researchers said that the lack of associations with gender may be due to the low number of female patients in this study.

“Findings from the present study indicate a need for continuing clinical and behavioral treatment approaches across the life course for people with FXS [fragile X syndrome],” the researchers wrote.

Future studies are needed to better understand these trajectories and to “inform treatment and support options for individuals with FXS and their families,” they added.