Associations between genotype, phenotype and behaviours measured by the Rett syndrome behaviour questionnaire in Rett...

Area of Science:

• Neuroscience
• Genetics
• Clinical Psychology

Background:

• Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by significant impairments, comorbidities, and distinct behaviors like hand stereotypies.
• The Rett Syndrome Behavioural Questionnaire (RSBQ) was developed to capture the behavioral and emotional spectrum of RTT.
• Limited understanding exists regarding the correlation between RSBQ scores and the genetic and clinical profiles of individuals with RTT.

Purpose of the Study:

• To investigate the associations between genotype, age, functional abilities (mobility, hand function), sleep patterns, and RSBQ scores in individuals with Rett syndrome.
• To determine if RSBQ scores reflect clinical severity or the specific behavioral phenotype in RTT.

Main Methods:

• A cross-sectional analysis utilized data from the Australian Rett Syndrome Database and the International Rett Syndrome Phenotype Database.
• Parent caregivers completed the RSBQ and the Sleep Disturbance Scale for Children, providing data on age, variant type, functional abilities, and comorbidities.
• Linear regression modeling was employed to analyze associations between RSBQ scores and independent variables.

Main Results:

• Data from 365 individuals with RTT revealed that younger children (2-12 years) exhibited higher mean scores for Total, Night-time Behaviour, and Fear/Anxiety compared to adults.
• Specific variants (p.Arg255* and p.Arg294*) were associated with higher Total, Night-time Behaviours, and Mood scores, respectively.
• Abnormal scores on the disorders of initiating and maintaining sleep (DIMS) and disorders of excessive somnolence (DOES) subscales were linked to higher Total RSBQ scores, unlike other clinical comorbidities.

Conclusions:

• The RSBQ effectively measures the behavioral phenotype in Rett syndrome, with significant associations found with sleep disturbances.
• RSBQ scores do not consistently reflect clinical severity in terms of functional abilities or common comorbidities, except for sleep issues.
• Future clinical trials for RTT should integrate the RSBQ with other measures to comprehensively assess core functions and associated comorbidities.