KBG syndrome mimicking genetic generalized epilepsy.

Abstract

KBG syndrome is a rare autosomal dominant disorder characterised by short stature, craniofacial dysmorphism and other developmental skeletal and dental anomalies such as macrodontia [1]. The acronym KBG was chosen to represent the initial of the surnames of the three original families described and epileptic seizures are a common feature [1,2,3]. In addition shyness, anxiety, autistic spectrum disorders and hearing loss have all been reported and most affected patients exhibit developmental delay and intellectual disability [1,4,5]. Although considered polygenic in nature, Genetic Generalized Epilepsy (GGE) typically occurs sporadically [6]. Early descriptions reported high concordance rates among monozygotic twins [7,8]. Descriptive reports highlighted consistent clinical and electroencephalographic (EEG) similarities in twin pairs. Because the clinical and EEG phenotypes are often striking and collectively pathognomonic, GGE is less frequently misdiagnosed compared to other subtypes of epilepsy. Nonetheless, GGE can be erroneously misdiagnosed in Glut-1 deficiency, CHD-2 mutations and focal epilepsy with a midline dipole [9,10]. We report a pair of monozygotic twins who were initially diagnosed with GGE on clinical and EEG grounds. Whole exome trio testing was undertaken in their teenage years when their epilepsy proved drug-resistant and atypical clinical features became more prominent. Mutations in the ANKRD11 gene confirmed a diagnosis of KBG syndrome. We report that mutations in the ANKRD11 gene may produce a clinical syndrome that closely simulates sporadic GGE.