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

Fetal Agenesis of the Corpus Callosum (ACC) Clinical Trial

— EXACC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03600792
• Other study ID #: NI18011J
• Status: Completed
• Start date: August 28, 2018
• Est. completion date: October 19, 2019

Study information

• Verified date: January 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: October 19, 2019
• Est. primary completion date: October 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Congenital Abnormalities
• Fetal Agenesis of the Corpus Callosum (ACC)

Intervention

Genetic:
• whole 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

Locations

Country	Name	City	State
France	Groupe Hospitalier Pitié-Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

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