Epilepsy in Inv Dup (15) Syndrome: Clnical and Electrophysiological Features in a Case Series of Four Patients

Objectives and Background: This study aims to review and contribute to electroclinical features of inverted duplication of proximal chromosome 15 (inv dup [15]) syndrome. Inv dup (15) syndrome results from the instability of chromosome region 15q11-q13 and is most frequently associated with autism spectrum disorders. Affected patients also typically present with developmental delay and intellectual disability, hypotonia, expressive, and comprehensive language disorders, movement disorders and epilepsy. All of these patients carry a supernumerary chromosome 15 marker resulting in tetrasomy 15q, a region that involves the critical for neurodevelopment genes: UBE3A and SNRPN. Although epilepsy is recognized as a major challenge in the management of inv dup (15) syndrome, electroclinical data are limited and heterogenic.

Methods: A 5-year retrospective review of clinical notes, electronic patient records, and (video) electroencephalographic recordings of patients followed in our department for epilepsy associated with inv dup (15) syndrome.

Results: Medical records of four patients were reviewed. Several ictal and interictal EEG recordings and long-term follow-up were available for all patients. The majority of recorded seizures were classified as generalized tonic seizures, often occurring in clusters. Other rare types of recorded seizures include clusters of spasms (characteristic tonic seizure a minima or tonic spasm pattern), atonic, and generalized tonicoclonic seizures. Electrophysiological findings consist of multiform abnormalities on a disorganized background activity. Extended diffuse beta rhythm activity is found in all patients’ EEG recordings and seems more prominent during epileptic manifestations.

Conclusion: We recognize in this case series a significant predominance of tonic seizures of variable duration. Although generalized tonic seizures have been described in patients with inv dup (15), previous reports refer to spasms as the most frequent type of seizures. The excess in beta rhythm activity is highlighted among other EEG abnormalities and could correspond to an electrophysiological bio-marker, supporting the relevant theory of Frohlich et al. An electroclinical pattern of generalized epilepsy with tonic seizures and predominant diffuse fast rhythms is thus outlined in these four patients with inv dup (15) syndrome. Prospective studies are needed in order to confirm reported electroclinical data and to establish genetic/prognostic correlations.

No conflict of interest has been declared by the author(s).