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Microcephaly Genetic Deficiency in Neural Progenitors (MICROFANC)

This study is currently recruiting participants. (see Contacts and Locations)
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: May 22, 2014
Last verified: February 2012
  Purpose

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

Condition
Microcephaly

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Microcephaly Genetic Deficiency in Neural Progenitors: Genotyping, Phenotyping and Functional Neuro-anatomy and Neurobiology Comparative Primitive Microcephaly (MCPH) and the Fanconi Anemia (FA)

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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)



Secondary Outcome Measures:
  • 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



Estimated Enrollment: 135
Study Start Date: October 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Microcephaly
Microcephaly Intellectual abilities Cranial MRI
FANCONI ANEMIA

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565005

Contacts
Contact: Alain VERLOES, PU-PH 0033140033618 alain.verloes@rdb.aphp.fr
Contact: Sandrine PASSEMARD, MCU-PH 0033140035306 sandrine.passemard@rdb.aphp.fr

Locations
France
Robert Debre Hospital Recruiting
Paris, France, 75019
Contact: Alain VERLOES, PU-PH    0033140033618    alain.verloes@rdb.aphp.fr   
Contact: Sandrine PASSEMARD    0033140035306    sandrine.passemard@rdb.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Alain VERLOES, PU-PH Assistance Publique - Hôpitaux de Parsi
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01565005     History of Changes
Other Study ID Numbers: P 100128
Study First Received: February 29, 2012
Last Updated: May 22, 2014
Health Authority: France: Committee for the Protection of Personnes

Keywords provided by Assistance Publique - Hôpitaux de Paris:
MCPH
FANCONI ANEMIA

Additional relevant MeSH terms:
Microcephaly
Congenital Abnormalities
Craniofacial Abnormalities
Malformations of Cortical Development
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Nervous System Diseases
Nervous System Malformations

ClinicalTrials.gov processed this record on November 27, 2014