Epilepsy & Treatment

Biography

Biography: Jehan Suleiman

Abstract

Genetic testing including next generation sequencing have been increasingly used in the diagnosis of children with neurological disorders, including severe epilepsies and epileptic encephalopathy, intellectual disability and unexplained motor disorders. Here we report two pediatric cases from different consanguineous Emirati families. They both had early onset global developmental delay, quadriplegia and growth restriction. In addition, they both had epileptic encephalopathy and West syndrome. Case one had microcephaly and optic atrophy but normal MRI, while case two had cortical malformation in the form of polymicrogyria. Case two also had ventilator dependency and respiratory failure. Homozygous mutations involving the WWOX gene were found on whole exome sequencing in both cases (deletion affecting exons 3 to 4 in case one, and splice-site mutation c.606-1G>A in case two). Parents were heterozygous for the involved mutations, which confirm an autosomal recessive pattern of inheritance. WWOX is a cytoplasmic protein involved in many cellular processes including growth, differentiation and tumor suppression. WWOX mutations are reported in different human cancers. More recently WWOX mutations were described in a few cases with spino-cerebellar ataxia associated with epilepsy and mental retardation, a case of severe syndrome of growth retardation, microcephaly, epileptic seizures, optic atrophy, retinopathy and early death, a case of spasticity microcephaly seizures optic atrophy and psychomotor retardation, which is very similar to our 2 cases. The findings in our patients expand the phenotype associated with WWOX genetic abnormalities and confirm previous associations with microcephaly spasticity psychomotor retardation seizures and more importantly as a gene associated with epileptic encephalopathy and West Syndrome.