- Balanced translocations and abnormal phenotypes : what is the relationship ?
Recent progresses of medical cerebral imaging (specifically magnetic resonance imaging or MRI) provided new insights into the field of unexplained mental handicap. Patients with severe mental retardation and/or epilepsy are usually having MRI examination. The development of new apparatus allows to identify anomalies of cortical development. Such anomalies can be correlated to the clinical signs that are present in the patient, especially for epilepsy. These abnormal images can be considered such as « cerebral dysmorphic features », allowing sub-classifications to be made out of the general population of idiopathic mental handicap. This lead to the identification of a number of new syndromes and the genetic basis of several of them has been identified (see below).
Currently, almost 40 different types of neuronal migration disorders have been described. Several of them are genetically heterogeneous, which means that more than one gene will cause the same phenotype. These data indicate that many genes will be responsible for such pathologies in humans. At the beginning of 2007, less than 20 of these genes had been identified. An important molecular genetics work is thus necessary to identify the currently unknown genetic defects.
We want to study this population of mentally retarded patients, often suffering from epilepsy, and presenting an abnormal brain development. Among these anomalies, we will focus specifically to the anomalies affecting the development of the cerebral cortex. The clinical and neuroradiological informations concerning these children and young adults are not currently enough integrated to be exploitable. We propose to systematically collect the available data. It will lead to refine the diagnosis and to initiate clinical and molecular research projects in the field of normal and abnormal human brain function. The animal models which are routinely used in neuroscience laboratories are not appropriate to identify this type of anomalies. Indeed, an abnormal organization of the cerebral cortex is not systematically looked for in animals whereas it is very classically done in humans. The added value of clinical research is thus particularly important for such a project.
Our project bring together neuropediatricians, clinical geneticists, molecular geneticists, neuroradiologists and neuropsychologists in a multidisciplinary approach. Our aim is to improve the quality of the care given to these families at several levels : diagnosis, genetic counselling and prognosis. In the meantime, this work will provide important data to study the development of the nervous system in humans and the natural perturbations to which it is subject.