The Cognitive Variability in NF1 and TSC Monozygotic Twins

NCT02436746 | Unknown

• 1 other identifier: MEC-2014-483
• Study Type: observational
• Target: 116
• Locations: 1 country
• Sites: 1

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.

Conditions

Neurofibromatosis Type I; Tuberous Sclerosis Complex

Keywords

Von Recklinghausen's disease; Bourneville's disease; Cognitive variability; Loss of heterozygosity

Outcome Measures

Primary Outcomes (1)

• Correlation of full intelligence quotient

  Depending on age and cognitive development: Bayley Scales of Infant Development (BSID-III) or Wechsler Scale of Intelligence (Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) or Wechsler Intelligence Scale for Children (WISC-III) or Wechsler Adult Intelligence Scale (WAIS-III) )

  1 day

Secondary Outcomes (6)

• Correlation of word reading ability

  1 day

• Correlation of attention problems

  1 day

• Correlation of behavioural problems

  1 day

• Correlation of autistic features

  1 day

• Correlation of visuospatial judgement (NF1 twins only)

  1 day

Study Arms (2)

Neurofibromatosis type I (NF1)

Monozygotic twin pairs with genetically confirmed Neurofibromatosis type I

Tuberous Sclerosis Complex (TSC)

Monozygotic twin pairs with genetically confirmed Tuberous Sclerosis Complex

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Monozygotic twin pairs with genetically confirmed Neurofibromatosis type I or Tuberous Sclerosis Complex

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC

Rotterdam, 3000 CA, Netherlands

RECRUITING

MeSH Terms

Conditions

Neurofibromatosis 1; Tuberous Sclerosis

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hamartoma; Neoplasms, Multiple Primary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Congenital Abnormalities

Study Officials

• Ype Elgersma, Prof.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ype Elgersma, Prof.

CONTACT

+31 10 7037739; y.elgersma@erasmusmc.nl

André Rietman, MSc.

CONTACT

+31 10 7043829; a.rietman@erasmusmc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Y. Elgersma

Study Record Dates

• First Submitted: April 29, 2015
• First Posted: May 7, 2015
• Study Start: April 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: May 7, 2015

Record last verified: 2015-05

Locations

NL (1)