1 - Serviço de Genética Médica, Centro Hospitalar e Universitário de Lisboa Central, Lisboa, Portugal
2 - Unidade de Cuidados Intensivos Neonatais, Centro Hospitalar e Universitário de Lisboa Central, Lisboa, Portugal
- 26ª Reunião Anual da Sociedade Portuguesa de Genética Humanas, reunião nacional, sob a forma de comunicação oral
Introduction: Congenital malformations and genetic disorders are a leading cause of infant morbidity and mortality in the developed world, particularly in critical ill infants. Aim: To investigate the prevalence of genetic disease in a level IV neonatal intensive care unit (NICU) by identifying and describing genetic diagnosis, testing methodologies, timing of diagnosis, and clinical utility.
Methods: A retrospective medical review of NICU patient referred for inpatient Genetics observation from 2019 to 2021. Results: In total 50 patients were referred to genetic evaluation. The main clinical indication for referral was multiple congenital anomalies (19/50, 38%), followed by neurological disease (12/50, 24%), isolated congenital anomaly (7/50, 14%), single system condition (7/50, 14%), and multisystem disease (5/50, 10%). In total 18 patients received a genetic diagnosis (36%) using a variety of methodologies. In 42% cases (21/50), genetic evaluation is still ongoing and 22% (11/50) were clinical discharged without a genetic diagnosis. Cytogenetic techniques were the first-tier test in 42% cases (21/50) with a diagnostic yield of 10% (2/21). Whole exome sequencing (WES) was applied in 52% (26/50), of which 73% (19/26) as a first-tier test, and 27% (7/26) as follow-up investigation. Globally, WES had a diagnostic yield of 46% (12/26). Other methodologies included: Sanger sequencing (6/50, 12%), MS-MLPA (1/50, 2%), 7-dehydrocholesterol (1/50, 2%) and PCR (1/50, 2%). The age at molecular diagnosis ranged between 36 days and 34 months. A significant majority of diagnosis were made after inpatient discharge (13/18, 72%). Additionally, 28% (5/18) infants received a genetic diagnosis during hospitalization that impacted clinical decision making. All cases received genetic counselling.
Conclusion: Genomic medicine has high diagnostic and clinical utility in critical ill patients, as it allows for an appropriate management, early decision-making, establishing patient prognosis and appropriate genetic counselling. Our study provides important data for further improvements to the genetic diagnostic odyssey of critical ill patients.
Palavras Chave: critical ill infants, WES, NICU, genomic medicine