Brief Title
The Cognitive Variability in NF1 and TSC Monozygotic Twins
Official Title
The Cognitive Variability in Neurofibromatosis Type I and Tuberous Sclerosis Complex Monozygotic Twins
Brief Summary
Both Neurofibromatosis type 1 (NF1) and Tuberous Sclerosis Complex (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, but is
generally assumed to be caused by modifier genes which regulate the affected pathways.
However, recent studies brought forward an alternative explanation for the phenotypic
variability. Post-mortem studies showed that second hit mutations causing loss of the second
('healthy') allele are more widespread than previously believed. These loss of heterozygosity
(LOH) mutations cause bi-allelic loss of the disease-linked gene and are known to cause the
gross of somatic features in both diseases (like neurofibromas and hamartomas). Hence, it
could be the stochastic occurrence of second-hit mutations in the brain are the cause of the
variable cognitive phenotypes.
To investigate to what extent these LOH mutations in the brain contribute to the phenotype
and to what extent this variation is due to genetic modifiers factors is unknown. The
investigators therefore propose to elucidate this variability by comparing the correlation of
cognitive features of monozygotic twins with NF1 or TSC to healthy twins in the population.
If modifier genes are the cause of the variability of cognitive features in NF1 and TSC the
investigators expect that the variability in cognitive tests in monozygotic twins is the same
as monozygotic twins in the healthy population. However, if the variability is caused by the
occurrence of LOH mutations, the investigators expect to have a lower correlation in our
monozygotic patients compared to the healthy twins.
Study Type
Observational
Primary Outcome
Correlation of full intelligence quotient
Secondary Outcome
Correlation of word reading ability
Condition
Neurofibromatosis Type I
Study Arms / Comparison Groups
Neurofibromatosis type I (NF1)
Description: Monozygotic twin pairs with genetically confirmed Neurofibromatosis type I
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
116
Start Date
April 2015
Completion Date
April 2017
Primary Completion Date
April 2017
Eligibility Criteria
Inclusion Criteria:
- The participant is part of a monozygotic twin pair (which is genetically confirmed);
- NF1 or TSC patients with a genetically confirmed diagnosis;
- Oral and written informed consent by participant in case ≥ 18 years of age.
- Oral and written informed consent by both caregivers and assent by participant in case
of minor participants.
Exclusion Criteria:
- A potential subject 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.
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Ype Elgersma, Prof., +31 10 7037739, [email protected]
Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT02436746
Organization ID
MEC-2014-483
Responsible Party
Principal Investigator
Study Sponsor
Erasmus Medical Center
Study Sponsor
Ype Elgersma, Prof., Principal Investigator, Erasmus MC
Verification Date
May 2015