Abstracts

Rationale: The development of the human cortex is regulated by a multitude of genes. Aberration in these genes may lead to brain malformations, which are an important cause of childhood epilepsy. One such gene is the L1 cell adhesion molecule (L1CAM) gene. L1CAM, a member of the immunoglobulin superfamily of CAMs, is expressed on the surface of glial cells and neurons in the developing nervous system and plays a crucial role in corticogenesis, likely by mediating axonal path finding and cell migration. Mutations in the L1CAM gene cause L1 syndrome, an X-linked disorder with a broad phenotypic spectrum including X-linked hydrocephalus, MASA (mental retardation, adducted thumbs, spastic paraparesis, agenesis of the corpus callosum) syndrome, X-linked agenesis of the corpus callosum, and spastic paraplegia type 1.  More than 200 disease-causing mutations of the L1CAM gene have been reported, but epilepsy has been described in only one mutation (duplication) of this gene. An electroencephalogram (EEG) has not been previously reported in a patient with a disease-causing mutation of L1CAM gene.  Methods: We report the clinical history and serial EEG findings in a 4 year old male with X-linked hydrocephalus due to a missense mutation(G698R) of the L1CAM gene. This case report provides the first description of EEG in patient with L1 syndrome, and the first description of epilepsy in association with this particular mutation of the L1CAM gene. Results: We report the case of a 4 year old male child who was born by C-section at 37 weeks of gestation to a 32 year old female (gravida 2, para 1). The child was born to non-consanguineous parents, and there was no family history of hydrocephalus. Obstetric ultrasound at 18 weeks of gestation detected hydrocephalus. MRI brain confirmed severe hydrocephalus due to aqueductal stenosis, at birth and a ventriculo-peritoneal shunt was placed on day 1 of life. During this hospitalization he underwent genetic testing for hydrocephalus and was found to have missense mutation of L1CAM gene (GA698R). At age 6 months, a routine EEG was performed for episodes of eye rolling, which was normal (Figure 1).  At age 11 months another routine EEG was performed for similar episodes of eye rolling and truncal arching. This EEG showed delta range slowing over in the right hemispheric chains, but no epileptiform discharges. The episodes were determined to be due to acid reflux (Sandifer Syndrome). Magnetic resonance imaging of the brain done at this time revealed holoprosencephaly, and hydrocephalus with preservation of cortical mantle. By the age of 1 the child had global developmental delay but no seizures were reported.  At age of 3 years 9 months he presented with episodes of involuntary limb movements and decreased awareness. A routine EEG was performed, revealing multifocal spikes along with a background consisting of  high amplitude (150-300 microvolt) delta activity with superimposed, high amplitude (120-160 microvolt) beta activity (Figure 2). There was no documented use of benzodiazepines or other sedative-hypnotic medications prior to this EEG. Given the abnormal EEG, and episodes of involuntary movements, the child was diagnosed with epilepsy. Conclusions: Epilepsy is a rare manifestation of L1CAM gene mutation. We report the first case of epilepsy in a patient with missense mutation (A698R) of the L1CAM gene, substantiating previous reports that this cell adhesion molecule may be associated with genetic epilepsy. The patient’s progression of EEG abnormalities provides insight into the natural history of L1 syndrome.  Funding: No funding was received in support of this abstract.