M owat-Wilson Syndrome (MWS) is a neurodevelopmental disorder characterized by intellectual disability (ID), Hirschsprung disease, agenesis of the corpus collosum, seizures, expressive language deficits, a distinct facial gestalt, congenital heart defects, and behavioral dysregulation, with a happy and social demeanor (Adam et al. 2006). It is caused by de novo heterozygous mutations in the ZEB2 gene, which is produced at high levels in postmitotic neocortical neurons and may play a role in determining neuronal cell fate in corticogenesis (Seuntjens et al. 2009). The behavioral phenotype associated with MWS was recently characterized in a systematic evaluation of 61 MWS patients (Evans et al. 2012). The MWS behavioral profile was then compared with contrast participants with ID of various etiologies. Individuals with MWS were found to have higher rates of several behaviors, such as being unrealistically happy or elated and underreacting to pain. However, overall rates of clinically significant psychopathology were similar to the general ID population at *30% (Evans et al. 2012).Evidence-based psychopharmacological approaches can be used to target behavioral and emotional symptoms in individuals with MWS. However, the evidence base is built on studies of individuals with ID of many etiologies (Handen and Gilchrist 2006). Reporting of anecdotal clinical successes and failures in the MWS population specifically is a first step to improving future treatment outcomes. To our knowledge, there are currently no reports in the literature on the psychopharmacological management of problem behaviors in patients with MWS. Therefore, we report our experience with a single patient in hopes that it may act as a starting point toward more precise behavioral management strategies for individuals with MWS.
Case ReportThe patient was a 5-year-old nonverbal girl with ID, seizures, behavioral dysregulation, hypoalgesia, and gastrointestinal motility difficulties. Pregnancy and birth occurred without complication. The patient rolled over at 4 months, walked at 16 months, and babbled at 6 months, but then lost her verbal language abilities until she started babbling again at 4 years of age. Her language comprehension was intact, but she is learning sign language to express herself. Her developmental course had been complicated by seizures, with early-onset absence seizures and later-onset myoclonic and atonic seizures. Serial head MRIs revealed trace thinning of periatrial white matter without progression. Exome sequencing revealed a c.73 + 1G > T pathogenic variant in the ZEB2 gene, which is predicted to disrupt the canonical splice site between exons 2 and 3.Psychotropic management was initiated by a child neurologist for seizure control and problem behaviors such as irritability, tantrums, aggression, and nighttime awakenings. In summary, levetiracetam was found to be helpful for seizure control, but was ultimately discontinued because of worsening aggression and nighttime awakenings. Ethosuximide, clobazam, and divalproex sodium w...