Microcephaly Genetic Deficiency in Neural Progenitors (MICROFANC)

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ClinicalTrials.gov Identifier: NCT01565005

Recruitment Status : Completed

First Posted : March 28, 2012

Last Update Posted : March 2, 2018

Sponsor:

Information provided by (Responsible Party):

Assistance Publique - Hôpitaux de Paris

Study Description

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

Condition or disease
Microcephaly

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:

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.

Study Design


Study Type :	Observational
Actual Enrollment :	98 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
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)
Actual Study Start Date :	October 2013
Actual Primary Completion Date :	December 2017
Actual Study Completion Date :	December 2017

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Fanconi anemia Autosomal recessive primary microcephaly

MedlinePlus related topics: Anemia

Genetic and Rare Diseases Information Center resources: Microcephaly Microencephaly Fanconi Anemia Congenital Aplastic Anemia Fanconi Syndrome

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
Microcephaly Microcephaly Intellectual abilities Cranial MRI
FANCONI ANEMIA

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures :

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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	3 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

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 mitomycine Mutation in one FANC gene

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01565005

Locations


France
Robert Debre Hospital
Paris, France, 75019

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators


Principal Investigator:	Alain VERLOES, PU-PH	Assistance Publique - Hôpitaux de Parsi

More Information


Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01565005 History of Changes
Other Study ID Numbers:	P 100128
First Posted:	March 28, 2012 Key Record Dates
Last Update Posted:	March 2, 2018
Last Verified:	February 2018

Keywords provided by Assistance Publique - Hôpitaux de Paris:


MCPH FANCONI ANEMIA

Additional relevant MeSH terms:


Fanconi Anemia Microcephaly Anemia, Hypoplastic, Congenital Anemia, Aplastic Anemia Hematologic Diseases Bone Marrow Diseases Genetic Diseases, Inborn DNA Repair-Deficiency Disorders	Metabolic Diseases Craniofacial Abnormalities Musculoskeletal Abnormalities Musculoskeletal Diseases Malformations of Cortical Development, Group I Malformations of Cortical Development Nervous System Malformations Nervous System Diseases Congenital Abnormalities

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