Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-

Migrating partial seizures of infancy, also known as epilepsy of infancy with migrating focal seizures, is a rare early infantile epileptic encephalopathy with poor prognosis, presenting with focal seizures in the first year of life. A national surveillance study was undertaken in conjunction with the British Paediatric Neurology Surveillance Unit to further define the clinical, pathological and molecular genetic features of this disorder. Fourteen children with migrating partial seizures of infancy were reported during the 2 year study period (estimated prevalence 0.11 per 100,000 children). The study has revealed that migrating partial seizures of infancy is associated with an expanded spectrum of clinical features (including severe gut dysmotility and a movement disorder) and electrographic features including hypsarrhythmia (associated with infantile spasms) and burst suppression. We also report novel brain imaging findings including delayed myelination with white matter hyperintensity on brain magnetic resonance imaging in one-third of the cohort, and decreased N-acetyl aspartate on magnetic resonance spectroscopy. Putaminal atrophy (on both magnetic resonance imaging and at post-mortem) was evident in one patient. Additional neuropathological findings included bilateral hippocampal gliosis and neuronal loss in two patients who had post-mortem examinations. Within this cohort, we identified two patients with mutations in the newly discovered KCNT1 gene. Comparative genomic hybridization array, SCN1A testing and genetic testing for other currently known early infantile epileptic encephalopathy genes (including PLCB1 and SLC25A22) was non-informative for the rest of the cohort.

Summary:Identification of focal cortical dysplasia (FCD) on magnetic resonance (MR) images of young children with refractory focal epilepsy is important, as surgical resection may offer improvement of seizure control and subsequent developmental progress. However, the MR appearances of malformations of cortical development may change during brain maturation. We report 4 children with refractory focal epilepsy, whose MR images in infancy showed localized cortical and subcortical signal abnormalities (hypointense on T 2 -weighted and hyperintense on T 1 -weighted images), suggestive of abnormal cortical development. The visibility of these lesions was significantly reduced on later MR images. Subtle blurring of the gray-white matter junction in these areas was the only indicator of cortical abnormality in 3 patients, which was recognized only after comparison with earlier images. Taylor-type FCD was subsequently confirmed in all patients, following surgical cortical resection of the lesions. MR images performed early within the first year of life in children with epilepsy are important to identify areas of FCD. The appearances of FCD on later scans can be very subtle escaping recognition, and conclusions may be misleading with respect to diagnosis and appropriateness of surgical treatment.

The prevalence of skin and internal malignancies was estimated from the general practitioners' notes of 2247 patients with psoriasis and 4494 age- and sex-matched controls. The prevalence of skin cancer in the psoriatics was 155% that of controls, but this was not significant at the 5% level. Subgroup analysis showed an increase in skin cancers in women (P < 0.05). There was no difference in the age of onset of skin cancers between psoriatics and controls and there was no evidence of a cumulative therapeutic risk. There was no difference in the prevalence of non-skin cancers between psoriatics and controls.

The outlook for children with VGM is significantly better since the advent of endovascular treatment. Decisions about the appropriateness and timing of treatment should be taken by an experienced multidisciplinary team.