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

Completed
Conditions
Infant, Newborn, Diseases
Neurologic Symptoms
Intensive Care Unit
Congenital Malformations
Interventions
Other: Genetic analyse by whole exome sequencing
Registration Number
NCT03831035
Lead Sponsor
University Hospital, Montpellier
Brief 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).

Detailed 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 & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
15 patients and both parents.Genetic analyse by whole exome sequencingThe patients are aged 12 months or under hospitalized in the ICU suffering from multiple congenital malformations and/or neurologic symptoms.
Primary Outcome Measures
NameTimeMethod
Yield of exome results given to the family before 16 days16 days maximum after inclusion

number of days between the collect sample and results

Secondary Outcome Measures
NameTimeMethod
Adjustment of medical care allowed by the exome diagnosis16 days maximum after inclusion

Any additions or deletions of a diagnostic exam, medical care specific to the diagnosed pathology or screening of a known complication

number of medical consultations in the year following inclusiona year after inclusion

number of medical consultations in the year

Duration of each step until the results (the analytical step, the bioinformatic step, the interpretation step).16 days maximum after inclusion

number of days between the collect sample and results

Diagnosis yield : identification of the etiology3 months

number of days between the collect sample and diagnostic confirmation

duration of hospital stay in the year following inclusiona year after inclusion

number of days of hospital stay in the year

Quantity of blood necessary to achieve diagnosis16 days maximum after inclusion

number of samples necessary to achieve diagnosis

Trial Locations

Locations (1)

Medical genetics Arnaud de Villeneuve

🇫🇷

Montpellier, Hérault, France

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