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Objective: MECP2 duplication syndrome (MECP2DS) is an x-linked recessive syndrome characterized by infantile hypotonia, severe neurodevelopmental delay, intellectual disability, progressive spasticity, recurrent infections, and seizures. More than 50% of cases have been associated with epilepsy. Seizure semiology and electroencephalogram (EEG) findings in these patients are poorly described. Methods: In this case series, the authors describe the electroclinical features of children with MECP2DS presenting to their institution. In addition, they reviewed seizure types and therapies used. Results: Eight out of 9 patients with MECP2DS developed epilepsy, with 56% having normal initial EEG. Generalized slowing with generalized and focal/multifocal discharges was the most common EEG pattern which is consistent with prior studies. Atonic seizure was the most common semiology. Majority were pharmacoresistant (63%). Conclusion: The goal of this case series is to better define the clinical and electrophysiological aspects of the epilepsy associated with MECP2 duplication syndrome and provide practical guidance regarding management.

Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder that causes stagnation of development in adolescence and neurodegeneration in early adulthood. Precision therapies, including gene transfer therapy, are in development with a goal of taking advantage of the slow clinical course. Understanding of disease natural history and identification of disease‐relevant biomarkers are important steps in clinical trial readiness. We describe the clinical features of a diverse population of patients with AGU, including potential imaging and electrophysiological biomarkers. This is a single‐center, cross‐sectional study of the clinical, neuropsychological, electrophysiological, and imaging characteristics of AGU. A comprehensive assessment of eight participants (5 Non‐Finnish) revealed a mean non‐verbal IQ (NVIQ) of 70.25 ± 10.33 which decreased with age (rs = −0.85, p = 0.008). All participants demonstrated deficits in communication and gross/fine motor dysfunction. Auditory and visual evoked potentials demonstrated abnormalities in one or both modalities in 7 of 8 subjects, suggesting sensory pathway dysfunction. Brain imaging demonstrated T2 FLAIR hypointensity in the pulvinar nuclei and cerebral atrophy, as previously shown in the Finnish AGU population. Magnetic resonance spectroscopy (MRS) showed a 5.1 ppm peak corresponding to the toxic substrate (GlcNAc‐Asn), which accumulates in AGU. Our results showed there was no significant difference between Finnish and Non‐Finnish patients, and performance on standardized cognitive and motor testing was similar to prior studies. Age‐related changes on functional assessments and disease‐relevant abnormalities on surrogate biomarkers, such as MRS, could be used as outcome measures in a clinical trial.

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