Corpus Callosum Agenesis and Intellectual Disability: Genetic and Phenotypic Characterization

Corpus callosum is the main midline brain structure connecting homologous cortical areas of both hemispheres. Corpus callosum agenesis or dysgenesis (CCA) can be diagnosed antenatally, either isolated or associated with other cerebral or extra-cerebral malformations. With an incidence of 1.8/10,000 newborn, CCA is often associated with chromosomal anomalies and mendelian syndromes. Even when CCA appears to be isolated, the neuro-developmental outcome is uncertain, with many children developing normally, and others having moderate learning disabilities or even severe ID. The genetic heterogeneity of complex CCA is large (CCA can be observed in more than 300 entities), but for many patients, no etiological diagnosis is known. Therefore, genetic counselling remains challenging in many cases. Recurrence is observed in almost 5% of cases, and for most patients with no etiological diagnosis, the disease is sporadic. These data suggest both recessive and dominant de novo inheritance.

This study aims, in a prospective cohort of 120 patients with CCA and intellectual disability:

1. To determine the nature and the frequency of characterized genetic abnormalities.
2. To determine the phenotypic spectrum of complex CCA
3. To perform SNP-array analyses (i) for patients without etiological diagnosis and (ii) for patients with an identified syndrome without molecular basis to clarify the genetic basis of CCA and to evaluate the contribution of this technique in these patients
4. To describe new clinical- genetic entities

Patients are recruited through pediatric neurology and genetics consultations in the reference and competence centers " intellectual disabilities of rare cause" and associated network called "DéfiSciences".

The workup will include for all patients :