Autism & Developmental

Brief report: aggression and stereotypic behavior in males with fragile X syndrome--moderating secondary genes in a "single gene" disorder.

Hessl et al. (2008) · Journal of autism and developmental disorders 2008
★ The Verdict

In fragile X males, the 5-HTTLPR long/long genotype is linked to higher aggression and stereotypy—consider genetic data when designing behavior plans.

✓ Read this if BCBAs working with boys with fragile X in clinic or school settings.
✗ Skip if BCBAs serving only neurotypical clients or adults without genetic diagnoses.

01Research in Context

01

What this study did

Smith et al. (2008) looked at 5-HTTLPR, a gene that moves serotonin in the brain.

They asked if different forms of this gene change how much boys with fragile X hit, kick, or rock and flap.

Doctors took cheek swabs and parents filled out behavior forms.

02

What they found

Boys with the long/long form showed the most hitting and rocking.

Boys with the short/short form showed the least.

The gene form acted like a dial that turned behavior up or down.

03

How this fits with other research

Brady et al. (2024) asked 774 caregivers the same question but looked at triggers, not genes.

They found loud rooms and worry caused the hitting, no matter the gene.

The two studies do not fight: genes set the risk, but sensory pain pulls the trigger.

Wilde et al. (2017) counted hitting in tuberous sclerosis and got similar rates, showing single-gene ills can share behavior blueprints.

04

Why it matters

You can’t change genes, but you can change the room.

If a boy with fragile X has the long/long form, plan for extra breaks, soft lights, and calm voices.

Add deep-pressure or chew tools when noise rises.

Share the gene note with the doctor; some medicines target the same serotonin path.

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→ Action — try this Monday

Check the file for any gene report; if it says L/L, add extra sensory breaks and keep the room calm before problem behavior starts.

02At a glance

Intervention
not applicable
Design
other
Sample size
50
Population
developmental delay
Finding
positive

03Original abstract

Although fragile X syndrome (FXS) is a single gene disorder with a well-described phenotype, it is not known why some individuals develop more significant maladaptive behaviors such as aggression or autistic symptoms. Here, we studied two candidate genes known to affect mood and aggression, the serotonin transporter (5-HTTLPR) and monoamine oxidase A (MAOA-VNTR) polymorphisms, in 50 males with FXS ages 8-24 years. Mothers and fathers of participants reported the frequency and severity of aggressive/destructive, self-injurious, and stereotypic behaviors. Polymorphism genotypes were unrelated to age and IQ. Results showed a significant effect of 5-HTTLPR genotype on aggressive/destructive and stereotypic behavior; males with FXS who were homozygous for the high-transcribing long (L/L) genotype had the most aggressive and destructive behavior, and individuals homozygous for the short (S/S) genotype had the least aggression. Those with the L/L genotype also had the highest levels of stereotypic behavior. There was no effect of MAOA-VNTR on behavior; however those with the high-activity, 4-repeat genotype were more likely to be taking SSRI or SNRI medication. This preliminary study prompts consideration of secondary genes that may modify behavioral phenotype expression in neurodevelopmental disorders, even those with a single gene etiology such as FXS.

Journal of autism and developmental disorders, 2008 · doi:10.1007/s10803-007-0365-5