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

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

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.

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