Microcephaly Genetic Deficiency in Neural Progenitors (MICROFANC)

This study is currently recruiting participants.
Verified February 2012 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01565005
First received: February 29, 2012
Last updated: November 12, 2013
Last verified: February 2012

February 29, 2012
November 12, 2013
October 2013
October 2016   (final data collection date for primary outcome measure)
Compare neuroradiological phenotype and cognitive functioning with other MCPH-related patients [ Time Frame: 3 years ] [ Designated as safety issue: No ]

The purpose of this study is to:

Compare neuroradiological phenotype and cognitive functioning of MCPH patients caused by ASPM mutations already characterized and published (Passemard et al. 2009a) with other MCPH-related patients (patients with MCPH1, WDR62, CDK5RAP2, CEP 152, CENPJ, STIL, or PCNT mutations)

Same as current
Complete list of historical versions of study NCT01565005 on ClinicalTrials.gov Archive Site
Establish a clear organizational chart for the diagnosis of primary microcephaly [ Time Frame: 3 years ] [ Designated as safety issue: No ]

I. Establish a clear organizational chart for the diagnosis of primary microcephaly from the detailed description of the patient's phenotype

II. Establish epidemiological data on the molecular genetic causes involved in human primary microcephaly

Same as current
Not Provided
Not Provided
 
Microcephaly Genetic Deficiency in Neural Progenitors
Microcephaly Genetic Deficiency in Neural Progenitors: Genotyping, Phenotyping and Functional Neuro-anatomy and Neurobiology Comparative Primitive Microcephaly (MCPH) and the Fanconi Anemia (FA)

The purpose of this study is to:

I. Compare neuroradiological phenotype and cognitive functioning of MCPH patients caused by ASPM mutations already characterized and published (Passemard et al. 2009a) with other MCPH-related patients (patients with MCPH1, WDR62, CDK5RAP2, CEP 152, CENPJ, STIL, or PCNT mutations)

II. Describe the neuro-radiological and cognitive phenotype of microcephalic patients suffering from Fanconi anemia, and compared them to subjects with:

  • Fanconi anemia but normal OFC (head circumference)
  • MCPH patients
  • Healthy control subjects Our hypothesis is that mutations in genes responsible of microcephaly impact differentially cortical brain development and functioning

Phenotyping study on 2 different cohorts of rare disease affected patients:

  • Group1: MCPH (including different MCPH subtypes)
  • Group2: Fanconi Anemia (with or without microcephaly)

Inclusion criteria:

Common to each group:

  • Age > 3 years
  • Access to french "Social Security"
  • No contraindication for MRI

Group1:

  • Primary microcephaly without gross malformation within or extra nervous central system
  • OFC < -2SD at birth and < -3 SD after age 6months
  • Mutation in one MCPH gene

Group2:

Proven Fanconi Anemia with:

  • Positive chromosome breakage blood test
  • One of the 3 following elements:

FANCD2 positive test Fibroblast sensitivity to mitomycin Mutation in one FANC gene

Control subjects:

  • No antecedent
  • Normal education

Aims:

  1. Description of neurological, neuropsychological and radiological phenotype for each group
  2. Phenotype comparison:

    • groups 1&2
    • group1 or 2 with control subjects
    • different MCPH subtypes within group1
    • with or without microcephaly within group2
  3. Epidemiological data on these rare diseases in our population

Protocol:

Patients from both groups and control subjects will be evaluated in CIC for 1 day ½. They will be examined by a child neurologist and a geneticist. All of them will have cranial MRI (1.5Tesla). Neuropsychological assessment will be performed (Wechsler scales) for patients and control subjects.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

Group1:

  • Primary microcephaly without gross malformation within or extra nervous central system
  • OFC < -2SD at birth and < -3 SD after age 6months
  • Mutation in one MCPH gene

Group2:

Proven Fanconi Anemia with:

  • Positive chromosome breakage blood test
  • One of the 3 following elements:

FANCD2 positive test Fibroblast sensitivity to mitomycine Mutation in one FANC gene

Microcephaly
Not Provided
  • Microcephaly
    Microcephaly Intellectual abilities Cranial MRI
  • FANCONI ANEMIA
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
135
October 2016
October 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

Patients aged ≥ 3 years:

  • Microcephalic phenotype consistent with MCPH (recruitment already done as part of a network GIS-Rare Diseases Institute). MCPH patients have already been selected in the cohort "Robert Debré."
  • Holders of a Fanconi anemia characterized in terms of cytogenetics, enzyme and/or molecular (patients in the cohort "Saint Louis" followed by the KRC rare aplastic anemia)
  • Healthy controls aged ≥ 5 years siblings of patients with Fanconi Anemia

Exclusion Criteria:

Patients with Fanconi anemia:

  • bone marrow < 3 years
  • Post-transplantation neurological complications
  • developmental, genetic or environmental additional pathology
Both
3 Years and older
No
Contact: Alain VERLOES, PU-PH 0033140033618 alain.verloes@rdb.aphp.fr
Contact: Sandrine PASSEMARD, MCU-PH 0033140035306 sandrine.passemard@rdb.aphp.fr
France
 
NCT01565005
P 100128
No
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Not Provided
Principal Investigator: Alain VERLOES, PU-PH Assistance Publique - Hôpitaux de Parsi
Assistance Publique - Hôpitaux de Paris
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP