Clinical Trial: Corpus Callosum Agenesis and Intellectual Disability

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Corpus Callosum Agenesis and Intellectual Disability: Genetic and Phenotypic Characterization

Brief Summary:

Corpus callosum agenesis or dysgenesis (CCA) is a major brain malformation (˜1/4000 births) presently diagnosed by prenatal ultrasonography. In about half of the cases, CCA is associated with other anomalies (complex CCA), which usually leads to medical abortion. Syndromes including a CCA are many (hundreds), most of which are also associated with intellectual deficiency (ID). Several genes are involved in such complex CCA. On the other hand, several studies pointed to the favorable cognitive outcome of individuals/fetuses with an apparently isolated CCA (ICCA) during pregnancy in about 70% of cases. However, there are still 30% of cases with ID or developmental delay. The precise incidence and severity of these disorders are presently unclear. Therefore, prenatal counseling of couples facing a prenatal diagnosis of ICCA is still elusive.

Our aims are to unravel the genetic causes of CCA by combining phenotypic and genetic analyses in a prospective cohort of patients with CCA and intellectual disability, in order to improve prenatal information.


Detailed Summary:

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 di
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: genetic abnormalities [ Time Frame: baseline ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: June 13, 2014
Date Started: January 2012
Date Completion:
Last Updated: June 18, 2014
Last Verified: June 2014