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.

Hyperexcitability and Homeostasis in Fragile X Syndrome

“…In addition, the patients usually respond well to anti-epilepsy medicine, and most of the patients enter seizure remission before adulthood (Musumeci et al, 1999 ; Berry-Kravis, 2002 ). Although seizures and epilepsy are easily controlled for most patients, these seizures are still considered one of the serious comorbidities of FXS, and the EEG pattern in FXS is used as one of the endophenotypes to guide personalized treatment (Cowley et al, 2016 ).…”

Of Men and Mice: Modeling the Fragile X Syndrome

“…Particularly in children, seizures are frequent as well, affecting about 45% of the adolescent patients between 1 year and 14 years of age (Cowley et al, 2016 ; Figure 1 ). After the age of 20, seizure activity decreases, resulting in an overall prevalence of about 24% (Sabaratnam et al, 2001 ), although there is considerable variation among studies.…”

“…After the age of 20, seizure activity decreases, resulting in an overall prevalence of about 24% (Sabaratnam et al, 2001 ), although there is considerable variation among studies. Interestingly, some data suggest that the attention deficits observed in FXS patients are related to seizure activity (Cowley et al, 2016 ).…”

Seizures in Fragile X Syndrome: Associations and Longitudinal Analysis of a Large Clinic-Based Cohort

“…Studies investigating the association of seizures with other disease features in FXS include a small cohort which showed a trend toward an increased rate of seizures in individuals who were also diagnosed with ASD ( 26 ) and a second small case series of 11 patients which suggested an association between epilepsy and attention problems ( 27 ). In the largest investigation of seizures in FXS involving 1,394 individuals assessed by a survey and 352 individuals assessed in clinic ( 19 ), 14% of males and 6% of females reported seizures.…”