Whole Exome Sequencing in Prenatal Diagnosis of Agenesis of the Corpus Callosum

Completed

• Conditions: Fetal Agenesis of the Corpus Callosum (ACC)

• Registration Number: NCT03600792
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2018-06-10
• Study First Submitted QC: 2018-07-16
• Study First Posted: 2018-07-26
• Study Start: 2018-08-28
• Primary Completion: 2019-10-19
• Study Completion: 2019-10-19
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-15
• Last Update Posted: 2021-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Technical success	5th week post diagnosis	Rate of technical success

Secondary Outcome Measures

Name	Time	Method
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 interrupt pregnancy	up to 4 months	Number of interrupted pregnancies
Parents decision to continue pregnancy	up to 4 months	Number of continued pregnancies

Trial Locations

Locations (1)

Groupe Hospitalier Pitié-Salpêtrière; 🇫🇷 Paris, France