To determine the variability of cognitive features in NF1 and TSC in the absence of genetic variability.
ID
Source
Brief title
Condition
- Other condition
- Chromosomal abnormalities, gene alterations and gene variants
- Cognitive and attention disorders and disturbances
Synonym
Health condition
psychological
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in correlation of full IQ between twin pairs with either NF1 or
TSC and healthy twins in the population.
Secondary outcome
Secondary outcome measures are the difference in correlation of word-reading
ability and attention problems between twin pairs with either NF1 or TSC and
unaffected twins in the general population.
Tertiary outcome measures are the correlations of visuospatial judgement and
behavioural problems in patients with NF1 and TSC.
Background summary
Both NF1 and TSC are highly heterogeneous diseases. Cognitive features seem to
vary widely even between family members carrying the same mutation. This
phenotypic variability is not well understood. A plausible explanation for the
phenotypic variability could be the stochastic occurrence of second-hit
mutations in the brain, causing bi-allelic loss of the disease-linked gene
(loss of heterozygosity; LOH). Indeed, recent post-mortem studies showed that
second hit mutations causing loss of the second (*healthy*) allele, are more
widespread thant previously believed . These LOH mutations are also known to
cause most of the somatic features in both diseases. However, to what extent
these LOH mutations in the brain really contribute to the phenotype, and to
what extent this variation is due to genetic modifiers and environmental
factors, remains unknown. We therefore propose to elucidate this measure of
variability by comparing the correlation of cognitive features between
monozygotic twins with NF1 or TSC to healthy twins with these correlations in
the general population. We hypothesize that due to the occurrence of second hit
mutations, the variability of cognitive features in NF1 and TSC monozygotic
twins is higher compared to monozygotic twins in the general population.
Study objective
To determine the variability of cognitive features in NF1 and TSC in the
absence of genetic variability.
Study design
Cross-sectional twin study
Study burden and risks
Patients and caregivers are invited for one study visit to the Erasmus
MC-Sophia, unless they would prefer a house call by the neuropsychologist. The
total visit duration for a participant will be approximately 3 hours. During
the visit the participant will be asked to complete several neuropsychological
tests and both the patient and the caregivers will be asked to fill in several
questionnaires assessing behavioural and attentional problems.
All measures require mild to moderate effort to complete. The risks of
participating in this study are negligible.
Wytemaweg 80
Rotterdam 3015CN
NL
Wytemaweg 80
Rotterdam 3015CN
NL
Listed location countries
Age
Inclusion criteria
Participants are part of a monozygotic twin pair (which is genetically confirmed), disease genetically confirmed (either NF1 or TSC1/TSC2 mutation), oral and written informed consent by participants older than 18 years old, and oral and written informed consent by both caregivers of children below 18 years old and assent by participants between 12 and 18 years old.
Exclusion criteria
A potential subjects of whom the twin sibling is not willing or able to participate in this study, will be excluded from participation in this study
Symptomatic brain pathology
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL49467.078.14 |