Clinical trial NCT03600792: Whole Exome Sequencing in Prenatal Diagnosis of Agenesis of the Corpus Callosum
Official title: Whole Exome Sequencing in Prenatal Diagnosis of Agenesis of the Corpus Callosum
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fetal Agenesis of the Corpus Callosum (ACC)
Keywords: Agenesis of the corpus callosum
whole exome sequencing
prenatal diagnosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-07-26
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Technical success
timeFrame: 5th week post diagnosis
Secondary outcomes:
measure: Genetic diagnosis
timeFrame: 5th week post diagnosis
measure: Technical failure
timeFrame: up to 4 months
measure: Delay to genetic diagnosis Result
timeFrame: up to 4 months
measure: Parents decision to continue pregnancy
timeFrame: up to 4 months
measure: Parents decision to interrupt pregnancy
timeFrame: up to 4 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière
Study officials:
affiliation: APHP
name: Héron Delphine, MD
role: PRINCIPAL_INVESTIGATOR
References: