P39 – 2771: Variable phenotype in epilepsy caused by KCNQ2 mutations

Abstract

Objective KCNQ2 mutations have been described in infants with benign familial neonatal seizures but also in cases of epileptic encephalopathy. The objective of our study is to investigate the phenotype of KCNQ2-related epilepsy. Methods We reviewed initial seizure types, EEG and MRI data of children with infantile onset epilepsy caused by KCNQ2 mutation followed in the Pediatric Epilepsy Unit in the University Hospitals of Leuven. Results We describe 10 infants diagnosed with 9 different heterozygote missense mutations in KCNQ2. Five cases had a familial history of neonatal seizures, 5 cases were de novo. Onset of epilepsy occurred before 2 months in all cases. The predominant seizure type was tonic with deviaton of the head and eyes in 6 patients, clonic in 4 patients and co-occurence of apnea with cyanosis in 4 patients. Normal background EEG was found in 3/5 familial cases. The infants with encephalopathy showed a severely abnormal background activity with a burst-suppression pattern in 2, multifocal epileptic activity in 2 and normal background EEG in 1 case. Neuro-imaging showed no abnormalities in 9 cases. Normal developmental outcome was seen in 4 familial cases, only 1 had mild developmental delay. The encephalopathies showed moderate developmental delay in 1 and severe developmental delay in 4 cases respectively. All epileptic encephalopathies could initially be classified as drug resistant, but at last follow-up 3 of them were seizure free on medication. Conclusion There is an important phenotypical variability in patients with KCNQ2-related epilepsy. Early start of epilepsy is common, but clinical and electrographical phenotype is very variable. Neuro-imaging is not contributive. Familial occurrence has a normal developmental outcome in most cases. The majority of the de novo mutations showed a bad developmental outcome. Our results further suggest that KCNQ2 should be screened for in the diagnostic workup of early onset infantile seizures. KCNQ2 mutations have been described in infants with benign familial neonatal seizures but also in cases of epileptic encephalopathy. The objective of our study is to investigate the phenotype of KCNQ2-related epilepsy. We reviewed initial seizure types, EEG and MRI data of children with infantile onset epilepsy caused by KCNQ2 mutation followed in the Pediatric Epilepsy Unit in the University Hospitals of Leuven. We describe 10 infants diagnosed with 9 different heterozygote missense mutations in KCNQ2. Five cases had a familial history of neonatal seizures, 5 cases were de novo. Onset of epilepsy occurred before 2 months in all cases. The predominant seizure type was tonic with deviaton of the head and eyes in 6 patients, clonic in 4 patients and co-occurence of apnea with cyanosis in 4 patients. Normal background EEG was found in 3/5 familial cases. The infants with encephalopathy showed a severely abnormal background activity with a burst-suppression pattern in 2, multifocal epileptic activity in 2 and normal background EEG in 1 case. Neuro-imaging showed no abnormalities in 9 cases. Normal developmental outcome was seen in 4 familial cases, only 1 had mild developmental delay. The encephalopathies showed moderate developmental delay in 1 and severe developmental delay in 4 cases respectively. All epileptic encephalopathies could initially be classified as drug resistant, but at last follow-up 3 of them were seizure free on medication. There is an important phenotypical variability in patients with KCNQ2-related epilepsy. Early start of epilepsy is common, but clinical and electrographical phenotype is very variable. Neuro-imaging is not contributive. Familial occurrence has a normal developmental outcome in most cases. The majority of the de novo mutations showed a bad developmental outcome. Our results further suggest that KCNQ2 should be screened for in the diagnostic workup of early onset infantile seizures.