074. Characteristics of Clinical Presentation in Genetic Pediatric Cavernous Malformations in Patients with CCM and KRIT1 Mutations

Authors: Emade Jaman

CCM1/KRIT1, CCM2, and CCM3 mutations genetically predispose patients to the development of cerebral cavernous malformations (CCMs). While often asymptomatic, seizures or other focal neurological deficits are common presenting symptoms. Here we describe characteristics of the clinical presentation between patients with mutations and those without.Methods: A retrospective analysis of a prospectively managed database of pediatric patients diagnosed with CCMs between 2003 and 2019 at a single institution was analyzed to identify 74 cases of CCM with a mean age of 9.6±5.5 years at diagnosis (male=41, 55.4%). 13 patients underwent genetic testing, and 6 patients were positively identified (Nf4 for CCM1/KRIT1, Nf1 for CCM2 and Nf1 for CCM3). Variables related to demographics and clinical presentation were collected.
There was no significant difference in the mean age between those with genetic cavernomas compared to sporadic, 7.2±6.5 years (Nf6) vs. 4.1±4.2 years (Nf7) (p=0.17), respectively. Seizures were the most common presenting symptom in both groups, 28.6% (n=2) in those with mutations and 50% (n=3) in those without (p=0.591). Patients with mutations presented with larger lesions on MRI imaging, 7.59 cm3 (range 0.73-26.78 cm3) vs. 0.34 cm3 (range 0.02-1.2 cm3) (p=0.041). Presentation with intracranial hemorrhage was more common in patients with mutations (83.3% vs. 14.3%, p=0.029), and was more likely in patients with multiple lesions, seen in 67% (Nf4) of patients with ?4 lesions, while in only 29% (Nf2) of patients with < 4 lesions. Multiple cavernomas were seen in 100% of mutation carrying patients (median=6.5, range 2-21), compared to 42.9% in those without (median=1, range 2-27) (p=0.069).
At presentation, patients do not significantly differ in clinical symptoms, however, pediatric patients with genetic predisposition are more likely to present with acute intracranial hemorrhage and larger lesions on MRI, with an increased bleeding risk associated with a higher number of lesions.