A national surveillance study in conjunction with the British Paediatric Neurology Unit was undertaken to further define the clinical, pathological and molecular genetic features of migrating partial seizures of infancy (MPSI), a rare early infantile epileptic encephalopathy with poor prognosis. In 14 patients reported during the 2 year study period, MPSI was associated with an expanded spectrum of clinical features including gut dysmotility and movement disorder, EEG features including hypsarrhythmia with infantile spasms and burst suppression, and novel brain imaging including delayed myelination, white matter hyperintensity and in one patient at autopsy, putaminal atrophy. Two further autopsied cases showed hippocampal gliosis and neuronal loss. Two patients had mutations in the KCNT1 gene, while genetic testing for other known early infantile epileptic encephalopathy genes (including PLCB1 and SLC25A22) was negative. [1]

COMMENT. Investigators at the Children’s Hospital Boston found that loss of PLCB1 function is one cause of malignant migrating partial seizures in infancy (MMPEI), but screening of further cases for PLCB1 deletions or mutations was negative. [2]

Investigators at University of Melbourne, Australia, screened 15 unrelated children with migrating partial seizures of infancy (MPSI) for mutations in several genes associated with infantile epileptic encephalopathies. One patient had a de novo SCN1A missense mutation, and MPSI is the most severe SCN1A phenotype to-date. Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. [3]

Nordli DR at Lurie Children’s Hospital of Chicago, in discussing epileptic encephalopathies in infants and children, notes that similar gene mutations have been found in several different epilepsy syndromes, and accurate classification of these severe epilepsies is important as the first step toward improved treatment and outcome. [4]

A complex V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy in two siblings reported from Radboud University Medical Centre, Nijmegen Centre for Mitochondrial Disorders, The Netherlands [5]. Exome sequencing revealed a heterozygous mutation in the ATP5A1 gene.

ADORA2A polymorphism predisposes children to encephalopathy with febrile status epilepticus in a study of 85 patients with acute encephalopathy. AA diplotype of ADORA2A is associated with a higher risk of developing seizures and excitotoxic brain damage. [6]