Clinical Trial: Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked

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 inno

Detailed Summary:
Sponsor: Hospices Civils de Lyon

Current Primary Outcome: Clinical phenotyping of neurodevelopment: acquisition age of early developmental skills (motor and language), and the adaptive skills profile (Vineland adaptive behavioral scale) [ Time Frame: 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).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Intellectual functioning assessment (Wechsler scale) [ Time Frame: 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.
  • Raven's Progressive matrices [ Time Frame: at inclusion (Day 1) ]
    The Raven's Progressives matrices test will allow to assess the non-verbal reasoning mental age of the patient
  • Peabody Picture Vocabulary Test Revised [ Time Frame: at inclusion (Day 1) ]
    The Peabody Picture Vocabulary Test Revised will allow to determine the Vocabulary age (receptive language) of the patient.
  • Edinburgh handedness test [ Time Frame: at inclusion (Day 1) ]
    The Edinburgh handedness test will assess the handedness of the patients.
  • Birth parameters: weight, height and head circumference and APGAR score [ Time Frame: 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).
  • Nisonger child behavior rating form [ Time Frame: 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.
  • Caregiver Burden Inventory Modified [ Time Frame: 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 (behavior assessment) [ Time Frame: 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.
  • Analogical visual reasoning task (eye-tracking assessment) [ Time Frame: 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.
  • Kinematic analysis of a grasping movement [ Time Frame: 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).
  • Structural neuroimaging by MRI [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: at inclusion (Day 1) ]
    The school curriculum will include the age at school entrance, and the type of school the child went to.


Original Secondary Outcome: Same as current

Information By: Hospices Civils de Lyon

Dates:
Date Received: June 29, 2016
Date Started: April 2011
Date Completion: April 2017
Last Updated: October 13, 2016
Last Verified: October 2016