Abstracts

Rationale: To detail a case of genetic epilepsy and describe novel electrographic findings associated with a de novo chromosome Xp11.22-p11.23 duplication.

Methods: Case Report.

Results: We present a case of a 43-year-old woman with longstanding epilepsy, developmental motor and intellectual delay, and schizophrenia in the setting of a de novo chromosome Xp11.22-p11.23 duplication. The patient was described as having hypotonia at birth and significant motor delays during development, as well as intellectual disabilities. Onset of staring spells was at age 3, consisting of episodes of staring into space, behavioral arrest, and loss of tone, occasionally leading to a fall. An EEG done at age 11 was reportedly abnormal and led to the diagnosis of epilepsy. An MRI brain did not reveal an epileptogenic focus but was notable for diffuse parenchymal volume loss. She was tried on several anti-seizure medications including levetiracetam and ethosuximide without success. She later developed hallucinations and psychosis requiring treatment with intermittent clozapine.

She was evaluated by medical genetics on multiple occasions with a working diagnosis of Cowden Syndrome. Whole exome sequencing ultimately revealed a de novo chromosome Xp11.22p11.23 duplication. Clinical features associated with this duplication include intellectual disability, epilepsy, and early-onset puberty. Genetic testing was also notable for several variants of uncertain significance, including a c.47C >G/p.Thr16Arg variant in a Cowden syndrome gene called SDHB.

A variety of electrographic abnormalities associated with chromosome Xp11.22p11.23 duplication have been previously described, including bilateral temporal-parietal and centro-parietal spike waves, generalized poly-spikes, and increased in epileptiform activity during sleep^[1,2]. Consistent with these reports, EEGs in this patient also demonstrated bifrontal predominant 1.5-3 Hz slowing with shifting laterality as well as occasional low amplitude sharp waves with maximal electronegativity at C4 and P4. In addition, several interictal recordings consistently demonstrated posterior predominant sharp waves and spike/slow wave complexes, with maximal electronegativity at O1-O2, which were consistently activated by intermittent photic stimulation. To our knowledge, this is a novel report of photic stimulation induced posterior discharges in a patient with chromosome Xp11.22p11.23 duplication, and may represent an electrographic feature characteristic of this genetic syndrome.

References:
1) Giorda et al. Complex Segmental Duplications Mediate a Recurrent dup(X)(p11.22-p11.23) Associated with Mental Retardation, Speech Delay, and EEG Anomalies in Males and Females. Am J Hum Genet. 2009 Sep 11; 85(3): 394–400. DOI:https://doi.org/10.1016/j.ajhg.2009.08.001

2) Broli M et al. Definition of the neurological phenotype associated with dup (X)(p11.22-p11.23). Epileptic Disord. 2011 Sep;13(3):240-51. doi: 10.1684/epd.2011.0462. PMID: 21926047.

Conclusions: There are a variety of unique electrographic abnormalities associated with chromosome Xp11.22-p11.23 duplication syndromes, including the photic stimulation induced epileptiform discharges exemplified by this case.

Funding: Please list any funding that was received in support of this abstract.: None.