fast exome for diagnosis of congenital conditions in infants under 12 months of age hospitalized in intensive care unit

Conditions: Infant, Newborn, Diseases; Congenital Malformations; Intensive Care Unit; Neurologic Symptoms

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).

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.

Eligibility criteria:
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

Keywords: fast trio exome multiple congenital malformation intensive care unit neurological distress