Fragile X Syndrome
Conditions
Brief summary
Individuals with Fragile X Syndrome show differences in how they understand and learn language from infancy. They frequently have lifelong delays in speech and language as well. In addition, they experience other auditory symptoms, including being very sensitive to certain sounds as well as being more sensitive than others to loud sounds. The underlying brain activity for sound perception and speech learning in Fragile X is not well understood, especially in the infant, toddler, and preschool years. This study uses behavioral assessment of speech and language abilities, neuroimaging, and hearing tests to understand how speech and hearing are different in children with Fragile X Syndrome.
Detailed description
Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism and is associated with extremely high risk for early delays in speech and language. While early childhood is essential for speech and language development, neural mechanisms for language impairments have been studied entirely in older children and adults with FXS. Therefore, markers for speech and language impairments are unavailable in young children with FXS to predict severity, test potential mechanisms, and track response to intervention. The investigators have identified a hallmark brain-based phenotype of hyperresponsiveness to sounds in adolescents and adults with FXS. This fundamental alteration in cortical responses to sound could influence early language delays, but this phenotype has not been explored in infants or toddlers with FXS. Specifically, in this study the investigators will use simultaneous EEG/fNIRS during presentation of simple speech, stories, and nonspeech sounds to quantify and localize auditory hypersensitivity and neural differentiation in 30 preschoolers with FXS. The investigators will assess specificity through comparison with 30 typically developing controls and 30 mental-age matched children with a history of premature birth and language delays.
Interventions
Two different speech sounds are played at the same sound intensity.
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
24 Months to 4 Years
Healthy volunteers
Yes
Inclusion criteria
* Diagnoses of Fragile X Syndrome, Typical Development, or History of Premature Birth * able to sit independently * English is spoken at home
Exclusion criteria
* For all participants: no seizures in the past 6 months * For typical development group and Fragile X group: not born prior to 32 weeks gestation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in tympanometric pressure profile in the inner ear | at single study visit between ages of 2-4 years inclusive | Wide Band Tympanometry is completed to measure variability in tympanometric pressure for left and right ears that may affect hearing profile. |
| Changes in hearing thresholds | at single study visit between ages of 2-4 years inclusive | Hearing thresholds in dB as assessed using Conditioned Play Audiometry (CPA) or Visual Reinforced Audiometry (VRA) dependent on child age and developmental ability. |
| Otoacoustic Emissions (OAEs) | at single study visit between ages of 2-4 years inclusive | Signals produced by excitation of hair cells in cochlea are measured for a range of frequencies. |
| Change in Mullen Scales of Early Learning | at single study visit between ages of 2-4 years inclusive | change in Mullen Scales scores (age-corrected) from baseline on all subscales, including Expressive Language, Receptive Language, FIne Motor, Gross Motor, and Visual Reception. T-Scores from the Mullen Scales of Early Learning (MSEL) have a mean of 50 and a standard deviation of 10. Range=20-80. Higher scores indicate more advanced developmental skills. |
| Changes in oxygenated and deoxygenated hemoglobin concentration in response to sounds in language regions of the brain | at single study visit between ages of 2-4 years inclusive | Relative increase in oxygenated versus deoxygenated hemoglobin for no sounds, low intensity sounds, and medium intensity sounds. Measured via functional Near Infrared Spectroscopy with optodes placed over frontal, temporal, and parietal language regions. |
| Changes in amplitude of mismatch negativity response during sound discrimination | at single study visit between ages of 2-4 years inclusive | Electroencephalography is measured over the scalp while participant listens to speech sounds with infrequent oddball stimuli. Amplitude of the P100 for all stimuli as well as amplitude of the mismatch negativity response (frequent minus infrequent response) as well as change in these metrics over development are tracked in all groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensory Profile 2 Attentional subtest | at single study visit between ages of 2-4 years inclusive | parent-report measure of child's awareness of and responses to sensory cues in their environment. |
| Sensory profile 2 Auditory Processing subtest | at single study visit between ages of 2-4 years inclusive | parent-report measure of child's behavioral responses to sounds in their environment |
Countries
United States
Contacts
Primary ContactElizabeth Smith, PhD
Backup ContactCraig Erickson, MD
Outcome results
None listed