Whole Exome Sequencing in Prenatal Diagnosis of Agenesis of the Corpus Callosum (EXACC)

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.

Study Overview

• Status: Completed
• Conditions: Fetal Agenesis of the Corpus Callosum (ACC)
• Intervention / Treatment: Genetic: whole exome sequencing (WES)

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 Type: Observational
• Enrollment (Actual): 31

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Groupe Hospitalier Pitie-Salpetriere

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

30 trios (fetus and both parents) with confirmed diagnosis of fetal ACC during the 2nd or 3rd trimesters of pregnancy and who wish to perform molecular prenatal sequencing by WES.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success	Rate of technical success	5th week post diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic diagnosis	Rate of genetic diagnoses	5th week post diagnosis
Technical failure	Rate of technical failures	up to 4 months
Delay to genetic diagnosis Result	Delay between the ACC diagnosis and genetic sequencing known genes responsible for ACC	up to 4 months
Parents decision to continue pregnancy	Number of continued pregnancies	up to 4 months
Parents decision to interrupt pregnancy	Number of interrupted pregnancies	up to 4 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Héron Delphine, MD, APHP

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2018
• Primary Completion (Actual): October 19, 2019
• Study Completion (Actual): October 19, 2019

Study Registration Dates

• First Submitted: June 10, 2018
• First Submitted That Met QC Criteria: July 16, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: prenatal diagnosis; Agenesis of the corpus callosum; whole exome sequencing
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathological Conditions, Anatomical; Nervous System Malformations; Congenital Abnormalities; Agenesis of Corpus Callosum
• Other Study ID Numbers: NI18011J

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No