Objective: To identify the value of pre-defined clinical predictors for genetic testing results in infantile developmental and epileptic encephalopathies (DEEs).

Methods: Two comparative study group designed; group I (n=127): patients with gene named DEEs, and group II (n=39): Whole exome sequencing (WES) was performed in all patients with unknown etiology. The following 16 independent risk factors were evaluated for negative genetic testing: gender, type of seizure, seizure frequency, age at seizure onset (neonatal, <2 years), presence of epileptic spasm and tonic seizure, genetic stigma, abnormal neurologic imaging, special EEG pattern, abnormal metabolic screening test, febrile seizure, status epilepticus, family history of epilepsy, morbidity, consanguinity, and intellectual status (Table 1).

Results: Six clinical predictors were defined for a negative genetic testing with univariate analysis: history of febrile seizure (hazard ratio [HR]: 5.974; 95% confidence interval [CI]: 1.361-26.226), age at seizure onset < 2 years (HR: 6.354; 95% CI: 1.442-28.007), presence of epileptic spasm (HR: 2.723; 95% CI: 1.301-5.702), presence of special EEG pattern (HR: 5,2; 95% CI: 1.718-15.738), comorbidity (HR: 2.622; 95% CI: 1.018-6.753), intellectual status (HR: 2.644; 95% CI: 1.209-5.786). However, all predictors except the history of febrile seizure were statistically significant in multivariate analysis.

Conclusion: This study revealed six predictors for a negative genetic testing in the presented infantile DEEs cohort. However, each clinical factors might an indicative of a well-defined electroclinical syndrome, or a gene named DEEs. Then, we considered to continue genetic testing with additional / new genetic testing modalities (WGS, RNA sequencing and genomic mapping analysis.

Seda Kanmaz
Ege University Medical Faculty
Turkey

Yavuz Atas
Ege University Medical Faculty
Turkey

Dilara Ece Toprak Dogan
Ege University Medical Faculty
Turkey

Cemile Busra Olculu
Ege University Medical Faculty
Turkey

Tugce Ince
Ege University Medical Faculty
Turkey

Ozlem Yilmaz
Ege University Medical Faculty
Turkey

Gursel Sen
Ege University Medical Faculty
Turkey

Selin Karatas
Ege University Medical Faculty
Turkey

Enise Avci Durmusalioglu
Ege University Medical Faculty
Turkey

Esra Isik
Ege University Medical Faculty
Turkey

Tahir Atik
Ege University Medical Faculty
Turkey

Ozgur Cogulu
Ege University Medical Faculty
Turkey

Gül Aktan
Ege University Medical Faculty
Turkey

Sarenur Gökben
Ege University Medical Faculty
Turkey

Sanem Yılmaz
Ege University Medical Faculty
Turkey

Hasan Tekgul
Ege University Medical Faculty
Turkey