Microcephaly Genetic Deficiency in Neural Progenitors: Genotyping, Phenotyping and Functional Neuro-anatomy and Neurobiology Comparative Primitive Microcephaly (MCPH) and the Fanconi Anemia (FA)
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Microcephaly
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 98
- Locations
- 1
- Primary Endpoint
- Compare neuroradiological phenotype and cognitive functioning with other MCPH-related patients
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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 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.
Investigators
Eligibility 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
Outcomes
Primary Outcomes
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)
Secondary Outcomes
- Establish a clear organizational chart for the diagnosis of primary microcephaly(3 years)