Clinical Trial: Microcephaly Genetic Deficiency in Neural Progenitors

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Microcephaly Genetic Deficiency in Neural Progenitors: Genotyping, Phenotyping and Functional Neuro-anatomy and Neurobiology Comparative Primitive Mi

Brief Summary:

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

Detailed Summary:

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
    Sponsor: Assistance Publique - Hôpitaux de Paris

    Current Primary Outcome: Compare neuroradiological phenotype and cognitive functioning with other MCPH-related patients [ Time Frame: 3 years ]

    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)



    Original Primary Outcome: Same as current

    Current Secondary Outcome: Establish a clear organizational chart for the diagnosis of primary microcephaly [ Time Frame: 3 years ]

    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



    Original Secondary Outcome: Same as current

    Information By: Assistance Publique - Hôpitaux de Paris

    Dates:
    Date Received: February 29, 2012
    Date Started: October 2013
    Date Completion: June 2017
    Last Updated: November 28, 2016
    Last Verified: October 2016