Fetal Agenesis of the Corpus Callosum (ACC)
Conditions
Keywords
Agenesis of the corpus callosum, whole exome sequencing, prenatal diagnosis
Brief summary
Agenesis of the corpus callosum (ACC) is one of the most frequent cerebral malformations and is now diagnosed prenatally in most cases. Prenatal counseling is then challenging because of uncertain neurodevelopmental outcome, depending on the genetic cause of ACC. Our purpose is to evaluate the feasibility of sequencing known genes responsible for ACC by whole exome sequencing (WES) in trio (fetus and both parents) when ACC is diagnosed during the pregnancy, in order to provide complete and loyal information on the intellectual prognosis for the fetus.
Detailed description
Agenesis of the corpus callosum (ACC) is one of the most frequent cerebral malformations. The neurodevelopmental outcome of patients with ACC is extremely variable, ranging from normal intelligence to severe intellectual disability (ID). When ACC is discovered during the prenatal period, prenatal counseling is challenging because of this uncertain neurodevelopmental outcome. Currently, only chromosomal analyses are performed in cases of prenatal diagnoses, which are expected to bring the diagnosis in only few cases. No molecular studies of genes implied in ACC with or without ID are performed. Then, the couples are in the difficult situation of continuing or interrupting the pregnancy without complete information about the aetiology of ACC. All patients will have a consultation with an obstetrician and consultations with a paediatric neurologist and a geneticist. The geneticist will explain WES and its issues. Both parents will have to provide informed consent for the study.
Interventions
GENETICwhole exome sequencing (WES)
WES analysis will be performed in the UF de Génomique du Développement (APHP, Pitié-Salpêtrière hospital), using DNA extracted from amniotic fluid for the foetus (also used for chromosomal studies) and DNA extracted from peripheral blood for both parents. There will be no supplemental invasive sampling for this study. The result of WES will be returned during a consultation with the geneticist and the associated prognosis will be explained in case of molecular diagnosis
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
FAMILY_BASED
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old * ACC diagnosed prenatally during the 2nd trimester of pregnancy, confirmed by ultrasound by a referee * Fetal sample (amniotic fluid, 10 ml) et blood samples of both parents (2 tubes of 5 ml EDTA) * Covered by social security * Written consent obtain for routine and research genetic analysis
Exclusion criteria
* Refusal to participate from one or both parents * Pregnancies obtained with gamete donation (trio sequencing not feasible) * If one parent is not available (trio sequencing not feasible) * Inability to understand the given information * One or both parents under juridical protection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Technical success | 5th week post diagnosis | Rate of technical success |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genetic diagnosis | 5th week post diagnosis | Rate of genetic diagnoses |
| Technical failure | up to 4 months | Rate of technical failures |
| Delay to genetic diagnosis Result | up to 4 months | Delay between the ACC diagnosis and genetic sequencing known genes responsible for ACC |
| Parents decision to continue pregnancy | up to 4 months | Number of continued pregnancies |
| Parents decision to interrupt pregnancy | up to 4 months | Number of interrupted pregnancies |
Countries
France
Outcome results
None listed