Axenfeld-Rieger Anomaly and Neuropsychiatric Problems—More than Meets the Eye

Abstract

Objective The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients. Case Study We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively. Conclusion We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease.

Spectrum of white matter abnormalities associated with FOXC1‐related disorders in two unrelated cases

“…Although white matter abnormalities and atrophy may become apparent with the physiological aging process, the involvement seen in Individual 1 is considerably more extensive and diffuse than what expected at age 59. All these observations are in line with previous reports in which children as young as 1 year-old presented clear CSVD (French et al, 2014) and diffusely extensive white matter abnormalities were found in teenagers (Saffari et al, 2020), thus suggesting that in FOXC1-related disorders age, disease duration, and brain abnormalities are not linearly correlated. Nevertheless, it is worth following patients with regular brain MRI studies.…”