Free Communications: Genetics

Abstract

Abstract *SumimasaYamashita, *HirokoIwamoto, *MichikoYamada, *MizueIai, *KaoriMasuko, *KazuyoWakabayashi, and †KenjiSugai *Kanagawa Children's Medical Center, Division of Child Neurology, Yokohama ; and †National Center of Neurology and Psychiatry, Musashi Hospital, Division of Child Neurology, Kodaira, Japan. Purpose: We encountered four cases of early myoclonic encephalopathy, consisting of two sets of siblings in two families. In family S, the elder sister is 7 years old now, severely handicapped and demonstrating both uncontrolled myoclonic and short tonic seizures as well as severe hepatic cirrhosis. The younger brother died at age 9 months. In another family O, the elder sister died at age 1 year, and the younger sister died at age 3 months. Each pregnancy was normal, and the deliveries were term, and all infants showed normal birth weight and normal head circumference. None of the infants was severely asphyxiated. Methods: The clinical record of these four cases revealed that the first seizure commenced within 1.5 months after birth, and seizure types were tonic spasms and myoclonic and clonic seizures. A suppression burst pattern was found in all cases at the beginning and then changed to focal or multifocal abnormalities thereafter. None of the cases showed hypsarrhythmia on EEG. In family S, both cases had minor anomalies such as characteristic facial appearances and finger overlapping. Results: Brain MRI showed severe brain atrophy in all cases but none of the cases showed cortical dysgenesis. In family O, the elder sister showed progressive cerebral and cerebellar atrophy, and the younger sister showed myelinating arrest of the cerebral white matter. Developmental milestones were arrested since the neonatal period in four cases. All cases had severe microcephalus, spastic tetraplegia, and severe mental retardation. Laboratory examination revealed no abnormal findings including CBC, chemistry, lactate, pyruvate, amino acids analysis, organic acids analysis, lysosomal enzymes assay using white blood cells, cerebrospinal fluid examination, and urinalysis. Chromosomal study was normal in all cases. Anticonvulsants such as oral high-dose phenobarbital, intravenous phenytoin for focal onset seizures, and zonisamide for apneic attacks were all effective to a moderate extent in some cases but did not reach complete seizure control. Autopsies were performed in two cases. Severe gliosis of cerebral white matter and marked dendritic expansions of cerebellar Purkinje cells were seen in both cases. No storage materials of neuronal and glial cells or laminar structural abnormalities of the cerebral cortex were found. Conclusions: It is important to differentiate from early infantile epileptic encephalopathy, which is characterized by severe asphyxia, brain anomaly, or cortical dysgenesis as a cause, tonic spasm in the seizure pattern of the onset, and alteration to West syndrome. Our cases did not fulfill these points. The main type of seizure was myoclonic or erratic myoclonia. Early myoclonic encephalopathy (EME) is known in cases of nonketotic hyperglycinemia or other inherited metabolic disorders as a cause of the disease. We could not detect metabolic abnormalities in the cases described. However, EME was suspected to have developed because of some genetic factors that might have influenced the development of the infantile nervous system.