Genetic Diagnosis in Neonatal Encephalopathy With Hypoxic Brain Damage Using Targeted Gene Panel Sequencing

Area of Science:

• Neonatal Neurology
• Medical Genetics
• Pediatric Neurology

Background:

• Neonatal encephalopathy (NE) is a severe neurological condition in newborns.
• Hypoxic-ischemic encephalopathy is a primary cause, but some NE cases have non-hypoxic origins.
• Identifying genetic causes is crucial for understanding NE beyond hypoxia-ischemia.

Purpose of the Study:

• To identify genetic variations contributing to neonatal encephalopathy (NE) with hypoxic brain damage.
• To explore genetic etiologies distinct from hypoxia-ischemia in NE.
• To investigate the diagnostic yield of genetic testing in these complex cases.

Main Methods:

• Retrospective analysis of 34 patients diagnosed with NE and hypoxic brain damage over 10 years.
• Exclusion criteria included prematurity, lack of hypoxic events, infections, and other complications.
• Comprehensive clinical and radiological data review was performed.

Main Results:

• Genetic diagnosis was achieved in 11 (32.4%) patients.
• Pathogenic variants were found in 9 genes, including CACNA1A, KCNQ2, SCN2A, SCN8A, STXBP1, NSD1, PURA, ZBTB20, and ENG.
• Personalized treatments, like sodium-channel blockers and ketogenic diets, showed some effectiveness.

Conclusions:

• Genetic analysis is valuable for diagnosing the etiology of NE with concurrent hypoxic brain damage.
• Identifying genetic causes can guide tailored therapeutic strategies.
• Genetic testing offers diagnostic insights irrespective of initial clinical presentation.