Background and Purpose
Neonatal encephalopathy (NE) is a neurological syndrome that presents with severe neurological impairments and complications. Hypoxic-ischemic encephalopathy is a major contributor to poor outcomes, being responsible for 50%–80% of admissions to neonatal intensive care units. However, some cases of NE accompanied by hypoxic brain damage cannot be solely attributed to hypoxia-ischemia. We aimed to identify diverse pathogenic genetic variations that may be associated with cases of NE accompanied by hypoxic brain damage rather than hypoxia-ischemia.
Methods
We collected data from 34 patients diagnosed with NE accompanied by hypoxic brain damage over a 10-year period. Patients with the following specific conditions were excluded: 1) premature birth (<32 weeks), 2) no history of hypoxic events, 3) related anomalies, 4) neonatal infections, 5) antenatal or perinatal obstetrical complications, 6) severe hypoxia due to other medical conditions, and 7) early death (within 1 week). A comprehensive review of clinical and radiological features was conducted.
Results
A genetic diagnosis was made in 11 (32.4%) patients, with pathogenic variants being identified in the following 9 genes:
CACNA1A
(
n
=2),
KCNQ2
(
n
=2),
SCN2A
(
n
=1),
SCN8A
(
n
=1),
STXBP1
(
n
=1),
NSD1
(
n
=1),
PURA
(
n
=1),
ZBTB20
(
n
=1), and
ENG
(
n
=1). No specific treatment outcomes or clinical features other than preterm birth were associated with the results of the genetic analyses. Personalized treatments based on the results of genetic tests were attempted, such as the administration of sodium-channel blockers in patients with
KCNQ2
or
SCN8A
variants and the implementation of a ketogenic diet in patients with
STXBP1
or
SCN2A
mutations, which demonstrated some degree of effectiveness in these patients.
Conclusions
Genetic analyses may help in diagnosing the underlying etiology of NE and concurrent hypoxic brain damage, irrespective of the initial clinical features.
