FMR1 Mutations Linked to Early Atypical Temperament, Study Shows

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by Alice Melão |

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fragile X, autism, motor skills

Mutations in the FMR1 gene are associated with atypical temperament that can emerge as early as infancy, particularly among infants with fragile X syndrome, a study has shown.

The study, “Infant Temperament in the FMR1 Premutation and Fragile X Syndrome,” was published in the Journal of Clinical Child & Adolescent Psychology.

Temperament is considered to be a result of emotional, attentional, and regulatory processes that guide individual responses to the surrounding environment. For decades, temperament traits have been viewed as an important and stable predictor of personality and psychological disorders.

More recent studies have tried to better understand the diagnostic potential of temperament among populations with genetic disorders that may alter neurological function.

Now, researchers explored early temperament traits in children with two genetic conditions caused by atypical CGG repeat expansions on the FMR1 gene — FMR1 premutation, characterized by 55 to 200 repeats, and fragile X syndrome, characterized by more than 200 atypical repeats.

While the FMR1 premutation condition is highly prevalent and has been associated with increased risk for pediatric autism, attention problems and anxiety, fragile X is a low-incidence disorder often associated with intellectual disability and severe co-occurring psychosocial conditions, particularly in males.

The study enrolled 22 infants diagnosed with FMR1 premutation, 24 infants with fragile X syndrome, and 24 typically developing children, ages 5.26 to 15.19 months.

To evaluate children’s temperament, researchers used the Infant Behavior Questionnaire-Revised, a 191-item measure by which parents rate their child’s behavior over the past two weeks. The questionnaire covered three core domains: surgency (characterized by high levels of activity and positive emotion, impulsivity, and engagement with the surrounding environment), negative affect (the experience of negative emotions and poor self-concept) and regulatory capacity.

Based on parents’ answers, the team found that each group of infants had different primary temperament domains.

Those who had fragile X syndrome were found to have lower surgency when compared to those in the control or FMR1 premutation groups. In particular, this group was generally rated lower than controls in several surgency subdomains, including activity level, approach, vocal reactivity, smiling, and laughter.

Fragile X syndrome infants also had lower perceptual sensitivity than children with FMR1 premutation, with additional trends toward lower activity level, approach, vocal reactivity, smiling, and laughter.

Those in the FMR1 premutation group also showed lower high-intensity pleasure and vocal reactivity than the control group.

Fragile X syndrome infants were also found to have lower negative affect than the control group, a trait difference that was more pronounced among fragile X syndrome children younger than 10.4 months.

The FMR1 premutation group also showed slightly lower negative affect than the control group.

The differences between groups regarding negative affect were found to be primarily driven by lower distress to limitations in fragile X syndrome patients. These children also had marginally slower recovery from distress and lower fear than healthy infants.

On the other hand, FMR1 premutation infants had lower distress to limitations and sadness compared to controls.

Regulatory capacity or its subdomains (duration of orienting, low-intensity pleasure, cuddliness, soothability) were found to be similar among all three groups.

This study has “provided the first known characterization of infant temperament in FMR1 premutation contrasted to fragile X syndrome and typically developing controls,” researchers stated. “These data suggest that FMR1 gene mutations are associated with atypical temperament that emerges as early as infancy, particularly among infants with [fragile X].”

According to the team, additional studies are necessary to examine “whether temperament may index emergent clinical risks in these populations.”