The Cognitive Variability in NF1 and TSC Monozygotic Twins

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.

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

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