Abstracts

Rationale: X-linked lissencephaly with ambiguous genitalia (XLAG) is included in the spectrum of phenotypic disorders caused by ARX gene mutations. Findings include neonatal refractory epilepsy, acquired microcephaly, severe psychomotor delay, agenesis of the corpus callosum, and male genotypes with abnormal genitalia. References are limited about the epileptic phenotype of these patients. For this reason we will describe the epileptic phenotype for our population based on clinical findings, seizure types, electroencephalography, MRI and biomolecular studies. Methods: A retrospective analysis of two tertiary centers of pediatric neurology databases was performed between January 2009 and March 2012. Four lissencephaly and ambiguous genitalia cases were found by clinical records assessment. The genetic analysis was oriented on the search of ARX gene mutations. Results: All four registered cases had microcephaly, agenesis of the corpus callosum, ambiguous gentialia and lissencephaly (3 with a posterior-to-anterior gradient and 1 with an anterior-to-posterior gradient). Three showed refractory epilepsy, chronic diarrhea and EEG pattern of burst-suppression, among others. Seizures types were: spasms (3/4), focal clonic (4/4), subtle (2/4) and generalized tonic (2/4). Three of 4 presented status epilepticus. A mutation was detected in the homeodomain of the ARX gene (2/3). Bioinformatic analysis strongly suggested pathogenicity. Conclusions: The neonatal refractory epilepsy, abnormal genitalia and lissencephaly presence is strongly associated to ARX gene mutation performing most of the times a neonatal epileptic encephalopathy with high incidence of morbidity.