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Duplications in Xq28 involving MECP2 have been described in patients with severe mental retardation, infantile hypotonia, progressive spasticity, and recurrent infections. However, it is not yet clear to what extent these and accompanying symptoms may vary. In addition, the frequency of Xq28 duplications including MECP2 has yet to be determined in patients with unexplained X-linked mental retardation and (fe)males with severe encephalopathy. In this study, we used multiplex ligation-dependent probe amplification to screen Xq28 including MECP2 for deletions and duplications in these patient cohorts. In the group of 283 patients with X-linked mental retardation, we identified three Xq28 duplications including MECP2, which suggests that approximately 1% of unexplained X-linked mental retardation may be caused by MECP2 duplications. In addition, we found three additional MECP2 duplications in 134 male patients with mental retardation and severe, mostly progressive, neurological symptoms, indicating that the mutation frequency could be as high as 2% in this group of patients. In 329 female patients, no Xq28 duplications were detected. In total, we assessed 13 male patients with a MECP2 duplication from six unrelated families. Moderate to severe mental retardation and childhood hypotonia was noted in all patients. The majority of the patients also presented with absent speech, seizures, and progressive spasticity as well as ataxia or an ataxic gait and cerebral atrophy, two previously unreported symptoms. We propose to implement DNA copy number testing for MECP2 in the current diagnostic testing in all males with moderate to severe mental retardation accompanied by (progressive) neurological symptoms.

Aicardi-Goutières syndrome (AGS) is a rare, progressive, autosomal recessive encephalopathy characterised by basal ganglia calcifications, chronic CSF lymphocytosis, and negative serological investigations for the common prenatal infections. The clinical profile is characterised by acquired microcephaly, mild to severe cognitive delay and dystonia. Epilepsy is usually not prominent. We report on a 19-year-old patient with an atypical clinical course, characterized by a relatively benign presentation at onset. Epilepsy with complex-focal seizures, possibly with a visual aura and sometimes with secondary generalization, started at the age of nine years. Clinical deterioration occurred later, and at the age of 17 years he experienced severe, generalized, myoclonic attacks lasting hours, which were partly controlled by the administration of piracetam.[Published with video sequences].

Purpose: Simultaneous interictal EEG and magnetoencephalography (MEG) recordings were used for noninvasive analysis of epileptogenicity in focal cortical dysplasia (FCD). The results of two different approach methods (multiple source analysis of averaged spikes and single dipole peak localization of single spikes) were compared with pre- and postoperative anatomic magnetic resonance imaging (MRI). Patients: We studied nine children and adolescents (age, 3.5–15.9 years) with localization-related epilepsy and FCD diagnosis based on MRI. Five patients underwent epilepsy surgery, two of them after long-term recording with subdural grid electrodes, and one after intraoperative electrocorticography. Methods: The 122-channel whole-head MEGs and 33-channel EEGs were recorded simultaneously for 25 to 40 min. Interictal spikes were identified visually and used as templates to search for similar spatiotemporal spike patterns throughout the recording. With the BESA program, similar spikes ( r > 0.85) were detected, averaged, high-pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatiotemporal source analysis with a multishell spherical head model. Peak activity from single spikes was modeled by single dipoles for the same subset of spikes. Source localization was visualized by superposition on T1-weighted MRI and compared with the lesion identified in T1- and T2-weighted MRI. In the five cases undergoing epilepsy surgery, the results were correlated with invasive recordings, postoperative MRI, and outcome. Results: In all cases, the analysis of averaged spikes showed a localization of onset- and peak-related sources within the visible lesion for both EEG and MEG. Of the single spikes, 128 (45%; total 284) were localizable at the peak in MEG, and 170 (60%) in EEG. Of these, 91% localized within the lesion with MEG, and 93.5% with EEG. In three of five patients operated on, the resected area included the onset zones of averaged EEG and MEG spike activity. These patients had excellent postoperative outcome, whereas the others did not become seizure free. Conclusions: Consistent MEG and EEG spike localization in the lesional zone confirmed the hypothesis of intrinsic epileptogenicity in FCD. [ABSTRACT FROM AUTHOR]