Realization of Sequencing of All Known Human Genes in Case of Detection of Cerebral, Renal or Ophthalmological Fetal Malformations During Pregnancy in Order to Make an Etiological Diagnosis and to Precise the Fetal Prognosis

Not Applicable

• Conditions: Rare Genetic Disease; Fetal Malformation; Pregnancy Related

• Registration Number: NCT04406480
• Lead Sponsor: University Hospital, Strasbourg, France

Brief Summary

Congenital malformations concern 3% of pregnancies; most of them can be seen during pregnancy. For some malformations, an invasive sample (trophoblast biopsy or amniocentesis) is proposed to search a chromosomal abnormality by the technique of DNA chip. However, some strongly suggestive signs of a genetic (and not chromosomal) pathology have a very low diagnostic rate with this technique. In the absence of an etiological diagnosis, the prognosis for the unborn child is very difficult to assess, as we can't know if the fetal malformation is really isolated or associted to other unseen features as part of a syndromic condition.

For some malformations strongly suggestive of a genetic condition, we propose to realize an exome (i.e. all coding parts of the genome) sequencing of the trio (child and the 2 parents) with a delivery time compatible with the emergency situation of a pregnancy (6 weeks maximum). We will apply bioinformatics filters to analyse only genes known to be involved in the malformation present in the unborn child and thus avoid the identification of variants in unrelated genes. These lists of genes have been previously validated by the Rare Disease Health Sectors and the affiliated diagnostic laboratories. The selected malformations are: 1) anomalies of the central nervous system (microcephaly (\<- 2DS) with anomalies of gyration, anomalies of the posterior fossa, anomalies of the midline except agenesis of the corpus callosum), 2) ophthalmological anomalies (microphthalmia, hyperplasia vitreous) and 3) renal abnormalities (large hyperechoic kidneys).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-26
• Study First Submitted QC: 2020-05-26
• Study First Posted: 2020-05-28
• Study Start: 2020-08-05
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-10
• Last Update Posted: 2020-11-13
• Primary Completion: 2021-09
• Study Completion: 2023-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• Father and mother of an unborn child past the age of majority
• Consent dated and signed by the mother and by the father
• Father and mother able to understand the objectives and risks of the study
• For the mother, pregnancy in progress (between 12 and 34 weeks)
• For the mother, pregnancy with the presence of a malformation on ultrasound, confirmed by a doctor from the multidisciplinary diagnostic prenatal center, entering into the indications retained for this study
• Clinical validation of the couple's eligibility by an expert for some of selected indications
• Father and mother affiliated to a social protection health

Exclusion Criteria

• Identified genetic or chromosomal abnormality explaining the observed malformation
• Inability to give informations to the father and / or mother (father or mother in emergency or life-threatening situation)
• Father and / or mother under the protection of justice
• Father and / or mother under guardianship or curatorship
• Nursing woman

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Diagnostic contribution of the exome sequencing in antenatal period in comparison with the chromosomal analysis (CGH-array) realized in current health care	13 months	Comparison of the number of genetic diagnoses made by exome sequencing and by CGH-array.

Secondary Outcome Measures

Name	Time	Method
Feasibility study of carrying out exome sequencing in the antenatal period in terms of time to deliver results	13 months	Time to results from the inclusion of the trio (in days) specifying the time for each step (reception, sequencing, bioinformatics analysis, interpretation) (in days)
Effects on pregnancy management and/or postnatal child care due to an etiological diagnosis	13 months	Percentage of antenatal and/or postnatal fetus/child care modified by the molecular result

Trial Locations

Locations (12)

CHu de Besançon; 🇫🇷 Besançon, France

CHU de Dijon; 🇫🇷 Dijon, France

Hospices Civils de Lyon; 🇫🇷 Lyon, France

Groupe Hospitalier Region Mulhouse Et Sud Alsace; 🇫🇷 Mulhouse, France

CHU de Nancy; 🇫🇷 Nancy, France

Hôpital d'Enfants Armand-Trousseau; 🇫🇷 Paris, France

Hôpital de la Pitié Salpêtrière; 🇫🇷 Paris, France

Hôpital Necker Enfants Malades; 🇫🇷 Paris, France

CHU de Reims; 🇫🇷 Reims, France

CHU de Rennes; 🇫🇷 Rennes, France

Scroll for more (2 remaining)