Abstract
KBG syndrome is characterised by developmental delay, dental (macrodontia of upper central incisors), craniofacial and skeletal anomalies. Since the identification of variants in the gene (ANKRD11) responsible for KBG syndrome, wider phenotypes are emerging. While there is phenotypic variability within many features of KBG syndrome, epilepsy is not usually markedly severe and movement disorders largely undocumented. Here we describe a novel early onset phenotype of dyskinetic epileptic encephalopathy in a male, who presented during infancy with a florid hyperkinetic movement disorder and developmental regression. Initially he had epileptic spasms and tonic seizures, and EEGs revealed a modified hypsarrhythmia. The epilepsy phenotype evolved to Lennox-Gastaut syndrome with seizures resistant to multiple anti-seizure therapies and the movement disorder evolved to choreoathetosis of limbs and head with oro-lingual dyskinesias. Previous extensive neurometabolic and imaging investigations, including panel-based exome sequencing were unremarkable. Later trio exome sequencing identified a de novo pathogenic heterozygous frameshift deletion of ANKRD11 (c.6792delC; p.Ala2265Profs*72). Review of the literature did not identify any individuals with such a hyperkinetic movement disorder presentation in combination with early-onset epileptic encephalopathy. This report expands the phenotype of ANKRD11-related KBG syndrome to include epileptic dyskinetic encephalopathy.