Motor phenotyping in a Greek cohort of patients with neonatal and infantile onset developmental and epileptic encephalopathy

Abstract

Background: Developmental and epileptic encephalopathy (DEE) includes diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. Patients often present with movement disorders (MD). This study aims to delineate the motor phenotype in a cohort of patients with DEE.

Methods: Retrospective review of 82 patients with DEE. MD type and distribution were documented and when available, video recordings were reviewed.

Results: Patients were classified into five etiological groups: 30.5 % had a likely genetic diagnosis, 29.3 % a confirmed genetic diagnosis, 18.3 % an inborn error of metabolism (IEM), 14.6 % an acquired brain lesion, and 7.3 % a brain dysplasia. Hyperkinetic MDs were present in 85.4 % of patients, including dystonia (48.8 %), stereotypies (22.0 %), chorea (20.7 %), hyperekplexia (15.9 %), tremor (14.6 %), and myoclonus (6.1 %). Parkinsonism was observed in 11 % of patients, ataxia in 8.5 % and multiple MDs in 50 %. Paroxysmal episodes of MD exacerbation occurred in 6 patients, and transient MD in 8. Dystonia was most frequent in patients with acquired brain lesions (p = 0.003). Parkinsonism was more frequent in patients with brain dysplasias and IEM (p = 0.043).

Conclusions: This study confirms the high frequency of hyperkinetic and combined MD in DEE, and identifies characteristic MDs in conditions such SCN8A, FOXG1 and ARX related DEE, as well as ataxia and tremor in STXBP1, SCN1A, MTRFR, KCTD7 and 15q111-13 deletion. Novel observations, include the occurrence of paroxysmal dyskinetic exacerbations in FOXG1, axial stereotypies in KCNQ2, hyperekplexia in cortical dysplasia and Parkinsonism in ECHS1 with DEE.

Keywords: Chorea; Dystonia; Epilepsy; Hyperekplexia; Movement disorders; Parkinsonism.