Abstracts

Rationale: The Human WWOX gene, which is located on a chromosomal fragile site (FRA16D) is considered a tumor suppressed gene and plays an important role in tumorigenesis. Little is known about its role in the developing nervous system. Mutations of WWOX have been described in one report of infantile intractable seizures and another report of epilepsy, cerebellar ataxia and mental retardation, both occurring within consanguineous families. We describe 3 patients from consanguineous family presenting with early infantile epileptic encephalopathy, spasticity, and progressive microcephaly with novel WWOX mutation. Methods: Cases notes review and molecular genetic investigations Results: The patients presented at 2 months of age with intractable focal seizures evolving to infantile spasms at 4/5 months of age and Lennox Gastaut syndrome at 12 months. Epilepsy was associated with early severe spasticity, progressive microcephaly, feeding problems and failure to thrive. EEG revealed generalised slowing evolving to hypsarythmia and multifocal discharges. MRI brain showed a hypoplastic corpus callosum, hypomyelination and generalised decrease in brain volume. Exome sequencing revealed a novel WWOX mutation: chr16_78458766 G>A. Fuctional studies confirmed the pathogenic role of this gene and give new insights of this gene in developing brain. Conclusions: Mutations in WWOX cause early onset epileptic encephalopathies, and a wide spectrum of CNS manifestations. This novel report of homozygous mutation expands the WWOX phenotype, supports an alternative role of WWOX gene and its crucial role in the developing nervous system