Abstracts

Rationale: Somatic mutations in focal epileptogenic lesions are increasingly recognized. Somatic mutation in the FGFR1 can cause encephalocraniocutaneous lipomatosis (ECCL), a rare neurocutaneous syndrome, manifesting with multiple system involvement including ocular, skin, bone, and intracranial lesions. Brain MRI features may show leptomeningeal angiomatosis and calcification, resembling features of Sturge-Weber syndrome. We report a teenager with refractory right temporo-parieto-occipital epilepsy in the setting of encephalocraniocutaneous lipomatosis. Methods: A 14-year-old boy with medically refractory epilepsy was evaluated for epilepsy surgery. Clinical and radiological features raised suspicion of encephalocraniocutaneous lipomatosis. Genetic analyses were done using both affected brain tissue and peripheral blood samples. Results: A 14-year-old right-handed boy began having seizures at the age of 12 years.  Seizures initially occurred as a cluster of generalized tonic-clonic seizures. Subsequently, he developed focal unaware seizures with periods of behavioral arrest and unresponsiveness. Seizures were frequent, at a rate of 1-4 per day, despite trials of 5 anti-seizure drugs, alone or in combination. He had also had autistic traits from early childhood and he reported memory dysfunction since the onset of epilepsy. Physical exam was significant for areas of subtle absent hair over the right frontal scalp, café-au-lait mark over the left abdomen, scattered nevi over the back, lipodermoids over the right eye, papular lesions of the right eyebrow, high palate, and absent right lower molars. He had a complex odontoma in the right mandible that required resection at the age of 8 years.   There was no facial port-wine stain. Neurological examination showed no focal deficits. Brain MRI showed marked leptomeningeal enhancement in right temporo-parieto-occipital junction, and right temporal lobe volume loss with a large right middle cranial fossa arachnoid cyst. Head CT showed calcification in the region of angiomatosis. Brain FDG-PET study showed extensive severe hypometabolism in the right posterior temporal and inferior parietal regions. Video EEG evaluation was consistent with right temporal epilepsy. Complete resection of the lesion had the highest chance for seizure freedom but was declined by the patient because of the risk of hemianopia. A large right temporal lobectomy with partial resection of angiomatosis led to substantial decrease in seizure burden. A second surgery, eight months later, led to near complete removal of the lesion and subjacent region. Due to persistence of seizures, a third surgery with extension of the resection to right posterior temporal occipital and inferior partial parietal lobe was done. He has remained seizure free at 2 year follow up. Genetic testing performed on the brain specimen showed an apparent de novo mosaic N546K variant in the FGFR1 gene, confirming the diagnosis of encephalocraniocutaneous lipomatosis. Exome analysis using peripheral blood DNA did not show any pathogenic variants, including the N546K variant in the FGFR1 gene, and a chromosomal microarray analysis was unrevealing. Spine MRI showed no lipomas, and echocardiogram was normal. Conclusions: Leptomeningeal angiomatosis with calcification in encephalocraniocutaneous lipomatosis shares shown resemblance to Sturge-Weber syndrome. In the presence of skin, ocular, and bone lesions, encephalocraniocutaneous lipomatosis should be considered. Complete resection of the lesion and peri-lesional tissue was necessary to achieve seizure freedom in this teenager. Funding: No funding