Abstracts

Rationale: Most patients with developmental and epileptic encephalopathy (DEE) are supposed to have genetic etiology, which has been uncovered with different methods of genetic analysis. Although chromosomal microarray analysis (CMA) has been broadly used in the patients with DEE, there are still short of data for the abnormal rates of CMA in the patients with DEE in different circumstances. We investigated the abnormal rate of CMA being based on seizure-onset age and specific epilepsy syndromes in the DEE patients without the known structural, metabolic or syndromic diagnoses.

Methods: The medical records of the 560 children (< 18 yr) getting CMA in our hospital between January 2013 and June 2021, were reviewed. Among them, the 146 patients with developmental delay and seizures were screened. The patients with major brain anomalies (N, 9), specific syndromes with archetypal features (N, 8), hypoxic or traumatic cerebral insults before seizure-onset (N, 7), and metabolic abnormalities (N, 4) were excluded. The cases with insufficient clinical data (N, 9) were also excluded. The rate of pathogenic and likely pathogenic results in CMA were estimated in total, which abnormal rate were further analyzed according to seizure-onset age, seizure-onset time comparing with delay-onset, specific epilepsy syndromes and organ systems with anomalies.

Results: Total 109 patients were finally enrolled to have unclassified DEE, among whom male were 66.1% (N, 72). The seizure-onset age was 48.0±52.6 months (mean±standard deviation). The rate of pathogenic and likely pathogenic results in CMA was 15.6 % (N, 17) in total, which varied according to subgroups of seizure-onset age: 0% (0/3) in neonatal period (< 1 months of age), 24.2% (8/33) in infantile period (1-11 months of age), 11.4% (5/44) in early childhood (1-5 yr), 5.3% (1/19) in late childhood (6-10 yr), and 30.0% (3/10) in adolescent period (11-17 yr). The abnormal rate of CMA according to seizure-onset time comparing with delay-onset, was 7.1% (2/28) in ‘before’, 20.0% (14/70) in ‘after’, and 12.5% (1/8) in ‘coincidentally’. The abnormal rate of CMA according to specific epilepsy syndrome was 15.4% (2/13) in ‘West syndrome’, 25.0% (1/4) in ‘epilepsy-aphasia spectrum disorder’, 13.0% (6/46) in ‘other predominantly focal or multifocal epilepsy’ and 28.6% (8/28) in ‘other predominantly generalized epilepsy’. The abnormal rate of CMA according to associated anomalies found in >10% of total patients, was 21.6% (8/37) in ‘minor brain anomalies’, 27.3% (6/22) in ‘facial dysmorphism’, 20.0% (3/15) in ‘genitourinary anomalies’, 46.2% (6/13) in ‘cardiovascular anomalies’, and 9.1% (1/13) in ‘endocrine anomalies’.

Conclusions: The abnormal rate of CMA in the patients with unclassified DEE was 15.6% in total. This rate was high in patients with seizures occurring in infancy (24.2%) or adolescence (30.0%), seizures occurring after delay-onset (20.0%), and ‘other predominantly generalized epilepsy’ (28.6%).

Funding: Please list any funding that was received in support of this abstract.: No.