Microcephaly Genetic Deficiency in Neural Progenitors

Microcephaly Clinical Trial

— MICROFANC  

Official title:

Microcephaly Genetic Deficiency in Neural Progenitors: Genotyping, Phenotyping and Functional Neuro-anatomy and Neurobiology Comparative Primitive Microcephaly (MCPH) and the Fanconi Anemia (FA)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01565005
• Other study ID #: P 100128
• Status: Completed
• Phase: N/A
• First received: February 29, 2012
• Last updated: March 1, 2018
• Start date: October 2013
• Est. completion date: December 2017

Study information

• Verified date: February 2018
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fanconi Anemia
• Microcephaly

Locations

Country	Name	City	State
France	Robert Debre Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare neuroradiological phenotype and cognitive functioning with other MCPH-related patients	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)	3 years
Secondary	Establish a clear organizational chart for the diagnosis of primary microcephaly	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	3 years