Microcephaly, Fanconi Anemia and Praxial Disorders (MicroFancII)

Fanconi Anemia (FA) is mentioned in children with congenital malformations including kidney, hart and skeletal malformations (absence or abnormal thumb or forearm), and bone marrow failure or myelodysplasia with a progressive onset in childhood or adulthood. No study has focused on microcephaly, a reduction in brain volume, which is present in 20% of children, and its consequences on cognitive and structural level of the brain. Since 2014, Robert-Debré's team has been interested in this functional cognitive and neuroanatomical approach trough a National PHRC. Preliminary results carried out on 12 children show that their intellectual efficiency was in the normal range for age. However, we noticed a significant difference between abilities in comprehension and verbal reasoning corresponding to what is expected for age, and the sensorimotor skills or fine motor praxia significantly reduced. These difficulties, graphically penalizing for these children, are not always explained by a skeletal malformation of the upper limb, suggesting that musculo-tendinous anomalies may be associated. The objectives of our project are: 1) to identify upper limb musculo-tendinous abnormalities and their functional consequences, 2) to determine if these abnormalities could influence the somatosensory representation of the upper limb at the cerebral cortical level. This project should help us to better understand the fine motor disabilities or developmental coordination disorder of these children, which penalize their learning, and provide them with adapted solutions.

Study Overview

• Status: Not yet recruiting
• Conditions: Fanconi Anemia
• Intervention / Treatment: Radiation: MRI of the hand and forearm,

Detailed Description

Our hypothesis is that children with FA present a developmental dyspraxia. This condition is very penalizing for children especially regarding graphic tasks, handwriting, whether or not they have skeletal malformations of the upper limbs. Consequences are fatigue because of energy expended trying to execute fine motor movements correctly.

Main objective:

To identify gesture dyspraxia in order to propose a targeted rehabilitation leading to national recommendations.

Main Evaluation Criteria :

1. measurement of fine motor praxia
2. quantification of dyspraxia

Secondary Objectives :

To identify the musculoskeletal or tendinous anomalies in the upper limbs of AF children and to assess their functional consequences.

To determine if these upper limbs abnormalities could influence the somatosensory map of this part of the body in the cerebral cortex.

Secondary Evaluation Criteria :

1. MRI of the hand and forearm, orthopedic examination and functional assessment
2. Previously obtained brain MRI data

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sandrine Passemard, MD; Phone Number: +331 40 03 36 91; Email: sandrine.passemard@aphp.fr

Study Locations

• France
  • Paris, France, 75019
    • Robert Drbré Hospital
    • Contact: Sandrine Passemard, MD; Phone Number: +331 40 03 36 91; Email: sandrine.passemard@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with Fanconi Anemia defined according to two of the following diagnostic criteria already included in the MicroFanc study:

   • Chromosome breakage test after exposure to an alkylating agent (mitomycin) on peripheral blood lymphocytes.
   • FancD2 test on lymphocytes or fibroblasts
   • sensitivity of fibroblasts to mitomycin
   • mutation in one of the FANC complementation genes (A, B, C, D1, D2, E, F, G, I, J, L, M, N)
2. Non-transplanted patients or patients at a distance from CSH transplant (>3 years)
3. Age ≥5 years of age at inclusion (minimum age of accessibility for neuropsychological tests and no need for sedation for MRI)

Exclusion Criteria:

Subjects for whom both parents have not agreed to participate in the research, or for whom MRI is contraindicated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Minor patients with Fanconi anemia; MRI of hands and forearm, neuropsychological and neuromotor tests	Radiation: MRI of the hand and forearm,; MRI of the hand and forearm,
Active Comparator: Minor controls; MRI of the hand and forearm, orthopedic evaluation, neuromotor tests of the upper limbs, praxies evaluation, neurocognitive evaluation	Radiation: MRI of the hand and forearm,; MRI of the hand and forearm,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
measurement of fine motor praxia	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Sandrine Passemard, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2021
• Primary Completion (Anticipated): July 15, 2022
• Study Completion (Anticipated): January 15, 2023

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): December 7, 2020
• Last Update Submitted That Met QC Criteria: November 30, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; DNA Repair-Deficiency Disorders; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Anemia; Microcephaly; Fanconi Syndrome; Fanconi Anemia
• Other Study ID Numbers: APHP200090; N° IDRCB: 2019-A03171-56 (Registry Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No