Case Report: A pediatric case of multifocal Streptococcus intermedius brain abscesses as the initial manifestation of SMAD4-associated juvenile polyposis-hereditary hemorrhagic telangiectasia overlap syndrome.

Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by epistaxis, telangiectasias, and arteriovenous malformations (AVMs). Clinical diagnosis of HHT is typically guided by fulfillment of the Curaçao criteria. HHT is a known risk factor for brain abscesses in the pediatric population, particularly in those with pulmonary AVMs, where intrapulmonary right-to-left shunting permits septic emboli to seed the brain. We report the case of a 9-year-old girl with asthma and chronic sinusitis who presented with 5 days of congestion, cough, and worsening headache in the setting of Coronavirus Disease 2019 infection. Due to persistent hypoxia and transient altered mental status, further evaluation was pursued, with brain magnetic resonance imaging revealing multiple ring-enhancing lesions and chest computed tomography (CT) demonstrating multiple pulmonary nodules. CT angiography confirmed diffuse pulmonary AVMs. Culture from a brain biopsy grew Streptococcus intermedius. Whole-genome sequencing identified a de novo heterozygous SMAD4 variant, supporting a molecular diagnosis of juvenile polyposis/HHT syndrome. This case illustrates an atypical presentation and early diagnosis of this syndrome, prompted by the incidental finding of multiple subclinical brain abscesses. It underscores the value of maintaining a broad differential and performing targeted diagnostic studies when encountering brain abscesses of unclear origin. Pulmonary AVMs should be considered as a potential etiology of brain abscess, particularly in patients with concomitant hypoxemia and when endocarditis has been excluded. Furthermore, genetic evaluation for HHT should be considered in pediatric patients with unexplained or multifocal brain abscesses, even when the Curaçao criteria are not met, as early recognition may help prevent neurologic complications.