Microcephaly Genetic Deficiency in Neural Progenitors

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:

• Description of neurological, neuropsychological and radiological phenotype for each group
• Phenotype comparison:

• groups 1&2
• group1 or 2 with control subjects
• different MCPH subtypes within group1
• with or without microcephaly within group2
• 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.

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