NAA10-related and NAA15-related neurodevelopmental (ND) syndromes present with intellectual disability, hypotonia, cardiac abnormalities, and delayed development. While data exists on the clinical manifestations of these conditions, there are few reports describing the neuroanatomical abnormalities present on imaging.

We aim to provide neuroimaging analyses for a subset of probands with NAA10- and NAA15-related neurodevelopmental symptoms and assess the severity and number of neuroanatomical anomalies and their associated functional impairments to better understand the pathophysiology of these disease processes.

Neuroimaging studies were obtained from 26 probands (18 with pathogenic variants in NAA10, 8 with pathogenic variants in NAA15) and evaluated. In depth medical histories were also collected on probands, including genetic testing results and developmental history. The Vineland 3 Adaptive Behavior Scale was also administered to assess functional status of the probands.

On average, individuals with NAA10-related ND syndrome had 5.7 anatomical abnormalities (standard deviation (SD) = 3.0), whereas those with NAA15-related ND syndrome had 2.8 (SD = 2.3, p = 0.02). Probands with a greater number of anatomical abnormalities tended to score worse on Vineland assessments. Structure and function were correlated 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 with NAA10-related ND syndrome.

This analysis of a cohort of probands with NAA10-related ND syndrome and NAA15-related ND syndrome by two neuroradiologists has established a range of subtle abnormalities. We hope these findings guide future research and diagnostic studies for this population.