Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked
- Conditions
- X-linked Mental Retardation
- Interventions
- Behavioral: Neuropsychological, cognitive and behavioral assessment
- Registration Number
- NCT02854956
- Lead Sponsor
- Hospices Civils de Lyon
- Brief Summary
X-linked Mental retardation (XLMR) represent 10% of the causes of mental retardation with a prevalence in both sexes around 1/296, i.e. 3.3 / 1000 births (Opitz et al., 1986). This heterogeneous group of XLMR includes dozens of rare diseases, some of them affecting only a few patients. Molecular diagnosis is currently available in France for 25 XLMR genes, within the national network of XLMR molecular diagnosis. However, whereas some syndromes such as Fragile X syndrome, are now well clinically defined, this is not the case for recently identified syndromes for which very few data is available, preventing clinicians to focus molecular diagnosis on a specific gene.
Therefore, this study aims to :
* Achieve a description of the clinical phenotype specific to each XLMR gene (Phase 1 of the study, n=200)
* Characterize the cognitive learning mechanisms and dysfunctional neural networks involved (Phase 2 of the study, n=75, i.e. 5 groups of 15 patients with a mutation in the same gene). These two elements constitute key steps to develop appropriate rehabilitation strategies and targeted pharmacological therapies.
Moreover, the impact of mental retardation on the primary caregiver within the family and the induced burden in terms of psycho-social, organizational and economic burden will also be assessed. These elements, directly related to the patient's environment, are very important to characterize in order to better understand the consequences of each gene mutation (Phase 3 of the study, n=283). For example, it is necessary to better understand the impact of Fragile X syndrome in terms of capacity and behavior, lifestyle, and health care needs of the patients While advancing knowledge allows to consider innovative therapeutics, the implementation of these therapeutics and assessment of their impact on the patients' life trajectory, require precise characterization of the population to be treated in medico socioeconomic terms.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 573
-
Age : from 2 to 60 years old
-
Having a pathogenic mutation of one of the X chromosome genes associated with :
- For boys : mental retardation (IQ<70), and/or developmental delay (DQ<70) and/or pervasive developmental disorder (autism, Asperger...)
- For girls : mental retardation (IQ<70), and/or developmental delay (DQ<70) and/or pervasive developmental disorder (autism, Asperger...) and/or specific learning disabilities
- patient or parents refusal to participate in the study
- genetic polymorphism in a X chromosome gene involved in mental retardation but not considered as pathogenic
- person refusing to be informed if an abnormality would be discovered during medical examination
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description X-linked Mental retardation Neuropsychological, cognitive and behavioral assessment This is an observational study which will allow to precisely describe the phenotype associated to each X-linked mental retardation gene. Control Group Neuropsychological, cognitive and behavioral assessment This group will be compared to X-linked mental retardation group in order to obtain a baseline on some cognitive tests.
- Primary Outcome Measures
Name Time Method Clinical phenotyping of neurodevelopment: acquisition age of early developmental skills (motor and language), and the adaptive skills profile (Vineland adaptive behavioral scale) at inclusion (Day 1) The primary outcome measure is composite and includes acquisition age of early developmental skills (motor and language), and the adaptive skills profile (Vineland adaptive behavioral scale). The Vineland adaptive behavioral scale performed during a semi-structured interview of the parents of the patient, will assess the adaptive behavior profile of the patient (including communication, daily living skills, socialization, motricity and the global adaptive score).
- Secondary Outcome Measures
Name Time Method Birth parameters: weight, height and head circumference and APGAR score at inclusion (Day 1) The birth parameters include weight, height and head circumference at birth, as well as the initial cardiac and pulmonary adaptation (APGAR score).
Peabody Picture Vocabulary Test Revised at inclusion (Day 1) The Peabody Picture Vocabulary Test Revised will allow to determine the Vocabulary age (receptive language) of the patient.
Analogical visual reasoning task (behavior assessment) at inclusion (Day 1) This paradigm (HCL/CNRS patented), appropriate for mentally retarded patients provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition.
Raven's Progressive matrices at inclusion (Day 1) The Raven's Progressives matrices test will allow to assess the non-verbal reasoning mental age of the patient
Edinburgh handedness test at inclusion (Day 1) The Edinburgh handedness test will assess the handedness of the patients.
Nisonger child behavior rating form at inclusion (Day 1) The Nisonger child behavior rating form will allow the assessment of behavior disorders including: conduct disorders, anxiety, hyperactivity, automutilation/stereotyped behavior, self-isolation/rituals, sensitivity/susceptibility.
Kinematic analysis of a grasping movement at inclusion (Day 1) This kinematic analysis of a grasping movement will allow us to study the effect of the orientation (+56°or -56°) and the type of pinch (thumb-index, thumb-middle finger and thumb-annular) on the movement duration and both the transport component (wrist acceleration and velocity peaks, latencies and amplitudes) and the grasp component (maximum grip aperture latency and amplitude and opposition axis).
Intellectual functioning assessment (Wechsler scale) at inclusion (Day 1) The Intellectual Quotient of the patient will be assessed using a Wechsler scale, adapted to the age of the patient. For patients younger than 3 years or too severely impaired to perform a Wechsler scale, the Brunet Lézine scale will be used.
Caregiver Burden Inventory Modified at inclusion (Day 1) The Caregiver Burden Inventory Modified will allow the assessment of the impact of mental retardation on the primary caregiver within the family.
Analogical visual reasoning task (eye-tracking assessment) at inclusion (Day 1) The eye-tracking analysis of this paradigm (HCL/CNRS patented) made it possible to identify the strategy used by participants to solve the task. Mentally Retarded patients are not able to explicitly explain the strategy they used to solve the task, but with eye-tracking analysis, we can understand how they performed the task, which is crucial information in order to help them improve their performance through remediation strategies.
Structural neuroimaging by MRI at inclusion (Day 1) Structural brain MRI analysis will determine if a specific morphological neuroanatomical pattern can be found for each X-linked mental retardation gene.
Functional neuroimaging by MRI at inclusion (Day 1) Functional brain MRI analysis will determine if patients with X-linked mental retardation have a specific functional neuroanatomical pattern associated to the reasoning task.
School curriculum: age and type of shool at inclusion (Day 1) The school curriculum will include the age at school entrance, and the type of school the child went to.
Trial Locations
- Locations (1)
Groupement Hospitalier Est - Hôpital Femme Mère Enfant - Service de neurologie pédiatrique
🇫🇷Bron, France