Microcephaly Genetic Deficiency in Neural Progenitors (MICROFANC)

• 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)

  
  

• 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

  
  

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.