Novel Compound Heterozygous Mutations in TBC 1 D 24 Cause Familial Malignant Migrating Partial Seizures of Infancy

Early‐onset epileptic encephalopathies ( EOEE s) are a group of rare devastating epileptic syndromes of infancy characterized by severe drug‐resistant seizures and electroencephalographic abnormalities. The current study aims to determine the genetic etiology of a familial form of EOEE fulfilling the diagnosis criteria for malignant migrating partial seizures of infancy ( MMPSI ). We identified two inherited novel mutations in TBC 1 D 24 in two affected siblings. Mutations severely impaired TBC 1 D 24 expression and function, which is critical for maturation of neuronal circuits. The screening of TBC 1 D 24 in an additional set of eight MMPSI patients was negative. TBC 1 D 24 loss of function has been associated to idiopathic infantile myoclonic epilepsy, as well as to drug‐resistant early‐onset epilepsy with intellectual disability. Here, we describe a familial form of MMPSI due to mutation in TBC 1 D 24 , revealing a devastating epileptic phenotype associated with TBC 1 D 24 dysfunction.