Abstracts

Rationale: Sotos Syndrome (SS) was initially described in 1964 based on major and minor criteria and later mutations and deletions of NSD1 were described in association with SS. Children with SS have seizures 15-50% of the time, primarily febrile seizures. Generalized tonic clonic seizures are the most common presentation, (47%). Seizures are usually controlled with monotherapy Anti-Epileptic-Drugs (AEDs), valproic acid being the most commonly used treatment. There have been no case reports of patients with SS having intractable epilepsy being placed on the ketogenic diet. Methods: This 3 year-old with dolichocephaly with a tall, prominent forehead, prominent orbital ridges, deep set eyes, epicanthal folds, downslanting palpebral fissures, thick columella, hypoplastic alae, retrognathia, deep philtrum, bifid uvula, mild pectus carinatum, and soft, translucent skin. He was born at 38 weeks without complication until 2 months of age when he presented with episodes of behavior arrest, bilateral arm extension, and upward eye deviation that were always provoked with a startle response. EEG at 4 months demonstrated a normal awake background, and intermittent frontal dominant generalized high voltage 3-3.5 HZ spike and wave activity, lasting up to 5-6 seconds with a provoked electroclinical seizure. All metabolic, and other genetic testing and initial MRI are normal. Repeat MRI at 2 years of age, demonstrated nonspecific foci of signal abnormality in the right frontal, left frontal, and right cerebellar white matter, most consistent with gliosis. Further evaluation revealed a heterozygous pathogenic missense variant in exon 18 of the NSD1 gene, p.Arg1952Trp (c.5854C>T) was identified. This is consistent with a diagnosis of SS. He was evaluated and determined to have mildly advanced bone age, within one standard deviation. Results: He was initially diagnosed with reflex epilepsy and started on levetiracetam. Where he did well for 1 year then presented with recurrent seizures, which were unprovoked. Levetiracetam was titrated and later topiramate was added as well as clobazam with the plan to initiate the ketogenic diet. Following addition of Clobazam and diet therapy he became seizure free and was subsequently weaned off levetiracetam and topiramate. Since initiation of the ketogenic diet he has done well with only mild constipation. Growth, typically excessive in SS, has been adequate at the 71st percentile with weight 76th percentile. Head circumference 99th percentile. Conclusions: With evolving genetic evaluation patients should be evaluated carefully to identify any known causes of their epilepsy. Disorders that were previously diagnosed base on clinical features may need re-evaluation as genetic variants are identified. In this case the child has no significant overgrowth despite of diagnosis of SS, which could be related to the cited side effect of slowed growth on the ketogenic diet however, given that no previous cases have been reported, this is largely unknown. Funding: n/a