Clinical trial NCT02854956: Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked
Official title: Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: X-linked Mental Retardation
Keywords: phenotype
X-linked mental retardation
neuronal networks
cognitive processes
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2016-08-04
Enrollment: 573
Sex: ALL
Minimum age (years): 2
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Clinical phenotyping of neurodevelopment: acquisition age of early developmental skills (motor and language), and the adaptive skills profile (Vineland adaptive behavioral scale)
timeFrame: at inclusion (Day 1)
Secondary outcomes:
measure: Intellectual functioning assessment (Wechsler scale)
timeFrame: at inclusion (Day 1)
measure: Raven's Progressive matrices
timeFrame: at inclusion (Day 1)
measure: Peabody Picture Vocabulary Test Revised
timeFrame: at inclusion (Day 1)
measure: Edinburgh handedness test
timeFrame: at inclusion (Day 1)
measure: Birth parameters: weight, height and head circumference and APGAR score
timeFrame: at inclusion (Day 1)
measure: Nisonger child behavior rating form
timeFrame: at inclusion (Day 1)
measure: Caregiver Burden Inventory Modified
timeFrame: at inclusion (Day 1)
measure: Analogical visual reasoning task (behavior assessment)
timeFrame: at inclusion (Day 1)
measure: Analogical visual reasoning task (eye-tracking assessment)
timeFrame: at inclusion (Day 1)
measure: Kinematic analysis of a grasping movement
timeFrame: at inclusion (Day 1)
measure: Structural neuroimaging by MRI
timeFrame: at inclusion (Day 1)
measure: Functional neuroimaging by MRI
timeFrame: at inclusion (Day 1)
measure: School curriculum: age and type of shool
timeFrame: at inclusion (Day 1)
Other outcomes:
Locations:
city: Bron
country: France
facility: Groupement Hospitalier Est - Hôpital Femme Mère Enfant - Service de neurologie pédiatrique
Study officials:
affiliation: Groupement Hospitalier Est - Hôpital Femme Mère Enfant - Service de neurologie pédiatrique
name: Vincent DESPORTES, Pr
role: PRINCIPAL_INVESTIGATOR
References: