title: Epileptic Electroencephalography Profile Associates with Attention Problems in Children with Fragile X Syndrome: Review and Case Series.
abstract: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and a variant of autism spectrum disorder (ASD). The FXS population is quite heterogeneous with respect to comorbidities, which implies the need for a personalized medicine approach, relying on biomarkers or endophenotypes to guide treatment. There is evidence that quantitative electroencephalography (EEG) endophenotype-guided treatments can support increased clinical benefit by considering the patient's neurophysiological profile. We describe a case series of 11 children diagnosed with FXS, aged one to 14 years, mean 4.6 years. Case data are based on longitudinal clinically-observed reports by attending physicians for comorbid symptoms including awake and asleep EEG profiles. We tabulate the comorbid EEG symptoms in this case series, and relate them to the literature on EEG endophenotypes and associated treatment options. The two most common endophenotypes in the data were diffuse slow oscillations and epileptiform EEG, which have been associated with attention and epilepsy respectively. This observation agrees with reported prevalence of comorbid behavioral symptoms for FXS. In this sample of FXS children, attention problems were found in 37% (4 of 11), and epileptic seizures in 45% (5 of 11). Attention problems were found to associate with the epilepsy endophenotype. From the synthesis of this case series and literature review, we argue that the evidence-based personalized treatment approach, exemplified by neurofeedback, could benefit FXS children by focusing on observable, specific characteristics of comorbid disease symptoms.
authors.affiliation: Brain Work Research Centre, Finnish Institute of Occupational HealthHelsinki, Finland; Cognitive Brain Research Unit, Cognitive Science, Institute of Behavioral Sciences, University of HelsinkiHelsinki, Finland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cowley
authors.affiliation: City of Helsinki Education Department Helsinki, Finland.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Kirjanen
authors.affiliation: Department of Clinical Neurophysiology, University Hospital of Helsinki Helsinki, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Partanen
authors.affiliation: Faculty of Medicine, Physiology, University of HelsinkiHelsinki, Finland; Autism Foundation in FinlandHelsinki, Finland.
authors.forename: Maija L
authors.initials: ML
authors.lastname: Castrén
keywords: attention deficit disorder; clinical case series; electroencephalography; endophenotype; fragile X syndrome; neurofeedback