Microcephaly Genetic Deficiency in Neural Progenitors

NCT01565005 | Completed

• 1 other identifier: P 100128
• Study Type: observational
• Target: 98
• Locations: 1 country
• Sites: 1

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

Conditions

Microcephaly

Keywords

MCPH; FANCONI ANEMIA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Establish a clear organizational chart for the diagnosis of primary microcephaly

  3 years

Study Arms (2)

Microcephaly

Microcephaly Intellectual abilities Cranial MRI

FANCONI ANEMIA

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• Patients with Fanconi anemia:
• bone marrow \< 3 years
• Post-transplantation neurological complications
• developmental, genetic or environmental additional pathology

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Robert Debre Hospital

Paris, 75019, France

Location

Related Publications (3)

• Gins C, Guimiot F, Drunat S, Prevost C, Rosenblatt J, Capri Y, Letard P, Khung-Savatovsky S, Mahi Henni MA, Elalaoui SC, Alison M, Guilmin Crepon S, Gressens P, Verloes A, Basto R, El Ghouzzi V, Passemard S. Radial Microbrain (Micrencephaly) Is Caused by a Recurrent Variant in the RTTN Gene. Neurol Genet. 2025 Mar 26;11(2):e200221. doi: 10.1212/NXG.0000000000200221. eCollection 2025 Apr.

  PMID: 40151166 DERIVED

• Ruaud L, Drunat S, Elmaleh-Berges M, Ernault A, Guilmin Crepon S; MCPH Consortium; El Ghouzzi V, Auvin S, Verloes A, Passemard S. Neurological outcome in WDR62 primary microcephaly. Dev Med Child Neurol. 2022 Apr;64(4):509-517. doi: 10.1111/dmcn.15060. Epub 2021 Sep 25.

  PMID: 35726608 DERIVED

• Nasser H, Vera L, Elmaleh-Berges M, Steindl K, Letard P, Teissier N, Ernault A, Guimiot F, Afenjar A, Moutard ML, Heron D, Alembik Y, Momtchilova M, Milani P, Kubis N, Pouvreau N, Zollino M, Guilmin Crepon S, Kaguelidou F, Gressens P, Verloes A, Rauch A, El Ghouzzi V, Drunat S, Passemard S. CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects. J Med Genet. 2020 Jun;57(6):389-399. doi: 10.1136/jmedgenet-2019-106474. Epub 2020 Feb 3.

  PMID: 32015000 DERIVED

MeSH Terms

Conditions

Microcephaly; Fanconi Anemia

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Alain VERLOES, PU-PH

  Assistance Publique - Hôpitaux de Parsi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 28, 2012
• Study Start: October 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: March 2, 2018

Record last verified: 2018-02

Locations

FR (1)