Microcephaly
Conditions
Keywords
MCPH, FANCONI ANEMIA
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.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare neuroradiological phenotype and cognitive functioning with other MCPH-related patients | 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
| Measure | Time frame | Description |
|---|---|---|
| Establish a clear organizational chart for the diagnosis of primary microcephaly | 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 |
Countries
France
Outcome results
None listed