Rates of rare copy number variants in different circumstances among patients with genetic developmental and epileptic encephalopathy.

backgroundMost patients with developmental and epileptic encephalopathy (DEE) have genetic etiology, which has been uncovered with different methods. Although chromosomal microarray analysis (CMA) has been broadly used in patients with DEE, data is still limited.

methodsAmong 560 children (<18 years) who underwent CMA in our hospital between January 2013 and June 2021, 146 patients with developmental delay and recurrent seizures were screened. Patients with major brain abnormalities, metabolic abnormalities, and specific syndromes were excluded. The rate of rare copy number variants (CNVs) was estimated in total and according to seizure-onset age, relation to first seizure with the diagnosis of developmental delay, epilepsy syndromes, and organ anomalies.

resultsAmong the 110 patients enrolled, the rate of rare CNVs was 16.4%, varying by seizure-onset age: 33.3% in three neonates, 21.2% in 33 infants, 13.3% in 45 early childhood patients, 5.3% in 19 late childhood patients, and 30.0% in 10 adolescents. In relation to the first seizure with the diagnosis of developmental delay, the rates were 3.7%, 22.2%, and 12.5% in "before", "after", and "concurrent" subclasses, respectively. The rates of rare CNVs were 16.7% in "other predominantly focal or multifocal epilepsy", 28.6% in "other predominantly generalized epilepsy (PGE)", and 15.4% in West syndrome. The rates were 27.8% in minor brain anomalies, 37.5% in facial dysmorphism, and 22.2%, 20.0%, and 57.1% in endocrine, genitourinary and cardiovascular anomalies, respectively.

conclusionThe rate of rare CNVs in patients with genetic DEE was 16.4% in total, which was higher in seizures occurring below the infantile period or after the diagnosis of developmental delay, in PGE, and in the presence of facial dysmorphism or cardiovascular anomalies.