Structural brain abnormalities in 12 persons with aniridia

Abstract

Background: Aniridia is a disorder predominately caused by heterozygous loss-of-function mutations of the PAX6 gene, which is a transcriptional regulator necessary for normal eye and brain development. The ocular abnormalities of aniridia have been well characterized, but mounting evidence has implicated brain-related phenotypes as a prominent feature of this disorder as well. Investigations using neuroimaging in aniridia patients have shown reductions in discrete brain structures and changes in global grey and white matter. However, limited sample sizes and substantive heterogeneity of structural phenotypes in the brain remain a challenge. Methods: Here, we examined brain structure in a new population sample in an effort to add to the collective understanding of anatomical abnormalities in aniridia. The current study used 3T magnetic resonance imaging to acquire high-resolution structural data in 12 persons with aniridia and 12 healthy demographically matched comparison subjects. Results: We examined five major structures: the anterior commissure, the posterior commissure, the pineal gland, the corpus callosum, and the optic chiasm. The most consistent reductions were found in the anterior commissure and the pineal gland; however, abnormalities in all of the other structures examined were present in at least one individual. Conclusions: Our results indicate that the anatomical abnormalities in aniridia are variable and largely individual-specific. These findings suggest that future studies investigate this heterogeneity further, and that normal population variation should be considered when evaluating structural abnormalities.

Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches

“…Aniridia associated brain abnormalities affect six structures of the midline: the optic chiasm, the olfactory bulb, the pineal gland, both anterior and posterior commissures and the corpus callosum ( Abouzeid et al, 2009 ; Bamiou et al, 2007 ; Free et al, 2003 ; Grant et al, 2017 ; Sisodiya et al, 2001 ). They can all be hypoplastic, or even absent – except for the optic chiasm and the corpus callosum.…”

Self-reported symptoms of everyday executive dysfunction, daytime sleepiness, and fatigue and health status among adults with congenital aniridia: a descriptive study

“…Individuals may markedly underreport their daily difficulties compared to objective results on neuropsychological tests, or they may overreport their competency compared to the reports of family members. While prior studies on aniridia patients have described deficits observed on neuropsychological tests (Heyman et al, 1999 ; Yogarajah et al, 2016 ) and developmental delay (Grant et al, 2017 ; Grant et al, 2021 ; Netland et al, 2011 ), complete neuropsychological testing can be difficult for individuals with aniridia due to their vision loss. In this regard, neuropsychological tests may not fully evaluate cognitive dysfunction in aniridia.…”

“…Central nervous system abnormalities have been identified in the anterior and posterior commissure, pineal gland, corpus callosum, and anterior cingulate cortex of individuals with aniridia (Berntsson et al, 2020 ; Ellison-Wright et al, 2004 ; Grant et al, 2017 ; Hanish et al, 2016 ; Yogarajah et al, 2016 ). In addition, adults with PAX6 -associated aniridia exhibited an age-related decrease in cortical thickness in the inferior parietal lobe, prefrontal areas, and premotor areas in both hemispheres compared to the control group (Yogarajah et al, 2016 ).…”

Psychoneurological Disorders in Children with Congenital Aniridia and <i>PAX6</i>-Associated Syndromes

“…Снижение интеллектуальных способностей у больных с врожденной аниридией (как правило, формирование умственной отсталости легкой степени) отмечено в еди-ничных исследованиях [33][34][35]. У пациентов с патогенными вариантами гена PAX6 также описано снижение функции вербальной рабочей памяти [26,31], что связывают с агенезией передней спайки головного мозга [26].…”