280 - Everolimus Therapy in Two Siblings of TCTA Triplet Set with Tuberous Sclerosis Complex

Poster Number: 280
Publication Number: 280.131

Daniel P. Schlepphorst, Levine Children's Hospital, Charlotte, NC, United States; Christina Marie. Hulgan, Levine Children's Hospital, Matthews, NC, United States; Chad Thomas. Jacobsen, Levine Children's Hospital, Charlotte, NC, United States

Background: Tuberous Sclerosis Complex (TSC) is an autosomal dominant neurocutaneous disorder where benign hamartomas develop in various organs. TSC phenotypes are highly variable and disease progression can lead to high morbidity and mortality. It is diagnosed clinically or by genetic testing. TSC1 and TSC2 genes are pathogenic variants resulting in overactivation of the mTOR pathway leading to tumor formation. Everolimus is an mTOR inhibitor used in some TSC patients for management of complex growing hamartomas or refractory seizures. 

Objective: Present a case of two siblings of a tri-chorionic tri-amniotic (TCTA) triplet set with TSC placed on Everolimus therapy.

Design/Methods: Case Report

Results: Two newborns from a TCTA pregnancy with prenatal concerns for TSC were born via cesarean section at 35 weeks 1 day. Fetal echocardiogram (Echo) showed cardiac masses in triplets 1 and 3 with concern for left ventricular outflow tract obstruction (LVOTO) in triplet 3. Postnatal screenings for TSC were performed. Triplet 1 had Echo with cardiac masses presumed to be cardiac rhabdomyomas; MRI Brain showed subependymal hamartomas and cortical and subcortical tubers; EEG showed subclinical seizures; MRI Abdomen showed renal and splenic cysts; Genetic testing was positive for TSC2 mutation. Seizures persisted despite various antiepileptic drug (AED) combinations including a midazolam drip, levetiracetam, zonisamide, clobazam, and oxcarbazepine. Hematology and Neurology consulted and recommended Everolimus therapy due to refractory seizures. Infant discharged on multiple AEDs and Everolimus, with a decrease in seizure frequency. Triplet 3 had an Echo confirming cardiac masses and LVOTO; MRI brain showed subependymal nodules and subcortical tubers; EEG was normal; MRI Abdomen showed simple renal cysts; Genetic testing positive for the same TSC2 mutation. Due to LVOTO, Hematology and Cardiology recommended treatment with Everolimus. After 1 week of therapy, trough levels were elevated so Everolimus was discontinued and never restarted as the cardiac masses decreased in size. 

Conclusion(s): Although Everolimus is FDA-approved for patients two years and older as adjunctive therapy for TSC-associated partial-onset seizures, these infants showed clinical improvement with the addition of Everolimus to their respective treatment regimens with a decrease in seizure activity in Triplet 1 and decrease in the cardiac rhabdomyoma size in both infants, although incidentally noted in follow-up echo for Triplet 1. Further observation will be needed to fully describe the long-term impact of Everolimus therapy on their disease progression.