Fast Exome for Diagnosis of Congenital Conditions in Infants Under 12 Months of Age Hospitalized in Intensive Care Unit

Intensive Care Unit Clinical Trial

— REUNIR  

Official title:

Fast Exome for Diagnosis of Congenital Conditions in Infants Under 12 Months of Age Hospitalized in Intensive Care Unit

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03831035
• Other study ID #: RECHMPL17_0387
• Status: Completed
• Start date: April 8, 2019
• Est. completion date: June 8, 2022

Study information

• Verified date: November 2023
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

An early diagnosis of congenital malformations and suspected genetic conditions in critically ill infants is essential to perform specific adapted care, prevention, and give proper genetic counseling. However, etiologies are various and each of them is individually very rare. Thanks to next-generation sequencing technologies, diagnosis time frames have drastically decreased and the investigators have observed an increase in diagnosis yields.

This study aims to evaluate the feasibility of fast trio exome sequencing (less than 16 days between informed consent signature and the consultation for results to the parents) in infants under the age of 12 months hospitalized in Intensive Care Unit (ICU).

Description:

This prospective study is the first French study aiming to evaluate the feasibility of fast trio exome sequencing (less than 16 days between informed consent signature and consultation for results presentation to the parents) in 15 infants under the age of 12 months hospitalized in the Intensive Care Unit. Included patients will have a year of follow-up examination.

The main evaluation criterion is the yield of exome results given to the family before 16 days. The secondary evaluation criteria are 1/ duration of each step until the results 2/ diagnosis yield : identification of the etiology 3/ adjustment of medical care allowed by the exome diagnosis 4/quantity of blood necessary to achieve diagnosis 5/ duration of hospital stay and number of medical consultations in the year following inclusion.

Exome sequencing will be performed on top of classical analysis ordinarily prescribed. Medical care will not be modified until exome results reception. After signature of informed consent, blood samples of the infant and both parents will be used for trio exome sequencing, which includes 3 steps : the analytical step (blood sample DNA extraction and high-throughput sequencing), the bioinformatic step, and the interpretation step.

The study includes four medical consultations:

1/consultation with a geneticist for inclusion, 2/consultation with a geneticist to give the exome results, 3/ consultation at 3 months after the results for the sanger-confirmation of the exome result, 4/ consultation at one year after the inclusion for medical follow-up.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 8, 2022
• Est. primary completion date: June 8, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 12 Months

Eligibility

Inclusion Criteria:

• Infant aged under 12 months , hospitalized in the ICU.

• Infant with multiple congenital malformations or neurological symptoms for which a genetic origin is suspected but undiagnosed genetically.

• Infant for whom both biological parents have given consent for the study, genetic analysis for themselves anf their child.

• Infant and parents registered in the French National health service

Exclusion Criteria:

• Absence of one or both parental sample.

• Precise genetic diagnosis made pre- or post-natally with chromosomal (I.e : Down syndrome), Sanger (i.e : infantile spinal amyotrophia) methylation (i.e : Prader-Willi syndrome) or triplet amplification (I.e : neonatal Steinert myotonia) studies.

• Strong clinical evidence for a with chromosomal (I.e : Down syndrome), Sanger (i.e :

infantile spinal amyotrophia) methylation (i.e : Prader-Willi syndrome) or triplet amplification (I.e : neonatal Steinert myotonia) studies.

• Impossibility for one or both parents to give his or her consent

Related Conditions & MeSH terms

• Congenital Abnormalities
• Congenital Malformations
• Infant, Newborn, Diseases
• Intensive Care Unit
• Neurologic Manifestations
• Neurologic Symptoms

Intervention

Other:
• Genetic analyse by whole exome sequencing
Exome sequencing requires analytic, bio informatic and interpretation steps.

Locations

Country	Name	City	State
France	Medical genetics Arnaud de Villeneuve	Montpellier	Hérault

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

References & Publications (29)

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Yield of exome results given to the family before 16 days	number of days between the collect sample and results	16 days maximum after inclusion
Secondary	Duration of each step until the results (the analytical step, the bioinformatic step, the interpretation step).	number of days between the collect sample and results	16 days maximum after inclusion
Secondary	Diagnosis yield : identification of the etiology	number of days between the collect sample and diagnostic confirmation	3 months
Secondary	Adjustment of medical care allowed by the exome diagnosis	Any additions or deletions of a diagnostic exam, medical care specific to the diagnosed pathology or screening of a known complication	16 days maximum after inclusion
Secondary	Quantity of blood necessary to achieve diagnosis	blood volume necessary to achieve diagnosis	16 days maximum after inclusion
Secondary	Quantity of blood necessary to achieve diagnosis	number of samples necessary to achieve diagnosis	16 days maximum after inclusion
Secondary	duration of hospital stay in the year following inclusion	number of days of hospital stay in the year	a year after inclusion
Secondary	number of medical consultations in the year following inclusion	number of medical consultations in the year	a year after inclusion