Fast Exome for Diagnosis of Congenital Conditions in Infants Under 12 Months of Age Hospitalized in Intensive Care Unit
Condition: Infant, Newborn, Diseases; Congenital Malformations; Intensive Care Unit; Neurologic Symptoms
MeSH terms: Neurologic Manifestations; Congenital Abnormalities; Infant, Newborn, Diseases
Study type: Observational

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.
    

Intervention name(s): Genetic analyse by whole exome sequencing
Intervention type(s): Other
Intervention description(s): Exome sequencing requires analytic, bio informatic and interpretation steps.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study includes 15 patients and both parents. The patients are aged 12 months or under
        hospitalized in the ICU suffering from multiple congenital malformations and/or neurologic
        symptoms
      
Biospecimen description: 
      It is a 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.
    
Keywords: Fast trio exome; Multiple congenital malformation; Intensive care unit; Neurological distress