Neuroanatomical Features of NAA10- and NAA15-Related Neurodevelopmental Syndromes

Abstract

BackgroundNAA10-related (Ogden Syndrome) andNAA15-related neurodevelopmental syndromes present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. While there is much data on the clinical manifestations of these conditions, there are few radiologic reports describing the neuroanatomical abnormalities present on imaging.ObjectiveOur goal was to provide neuroimaging analyses for a subset of probands withNAA10-andNAA15-related neurodevelopmental symptoms and assess severity, common radiologic anomalies, and changes over time to better understand the pathophysiology of these disease processes.Materials and MethodsNeuroimaging studies from 26 probands (18 with pathogenic variants inNAA10, 8 with pathogenic variants inNAA15) were collected and analyzed. Size of the cerebrum, brainstem, and cerebellum, as well as myelination, brain malformations, globus pallidus hyperintensity, brain lesions, 4th ventricle size, tegmentovermian angle, cisterna magna size, pituitary size, olfactory tract, palate arch, and choroid plexus abnormalities were analyzed. In depth medical histories were also collected on all probands, including genetic testing results and social, cognitive, and developmental history. The Vineland 3 Adaptive Behavior Scale was also administered to the parents to assess functional status of the probands.ResultsOn average, individuals with Ogden Syndrome had 5.7 anatomical abnormalities (standard deviation (SD) = 3.0), whereas those with NAA15 related neurodevelopmental syndrome had 2.8 (SD = 2.3) (p = .02). Probands who had more anatomical abnormalities tended to score worse on Vineland assessments, suggesting a possible correlation between the two. Structural-functional anatomic differences seen were preserved such that individuals with greater defects on, for example, motor regions of their scans tested worse on motor portions of the Vineland. Probands followed longitudinally demonstrated several changes between scans, most commonly in the cerebellum, brainstem, and degree of myelination. Such changes were only observed for probands withNAA10variants in our cohort.ConclusionDespite clinical imaging being reported as being predominantly “normal” during routine clinical care, this analysis of a cohort of patients withNAA10-related (Ogden Syndrome) andNAA15-related neurodevelopmental syndrome by one neuroradiologist has established a range of subtle abnormalities. We hope these findings guide future research and diagnostic studies for this patient population.