PMC8512218_01
PMC8512218_02
PMC8512218_03
Changes in brain MRI findings with age. Panels show axial images of
fluid-attenuated inversion recovery (FLAIR) brain MRI from 1 year 8 months
to 6 years 2 months of age. Images were obtained at 1 year 8 months (A and
H), 2 years 11 months (B and I), 3 years 7 months (C and J), 4 years 1 month
(D and K), 4 years 6 months (E and L), 5 years 1 month (F and M), and 6
years 2 months (G and N). White matter dystrophy was initially observed
predominantly in the occipital lobe, and the lesion gradually spread to the
corpus callosum ampulla, brainstem, and basal ganglia. Cerebral and
cerebellar atrophy with a predominance in the vermis was also progressive
with age.
10.1177_2329048X211048613-fig1.jpg
PMC8512218_03_10.1177_2329048X211048613-fig1.jpg
fig1-2329048X211048613
T2-weighted hyperintensity in the deep white matter of the occipital lobe, cerebral peduncle, and pyramidal tract of the brainstem (Figure 1A-C, H-J). The thalamus and basal ganglia remained normal in the early stages of the disease, until 2 years of age. T2-weighted hyperintensity in the white matter gradually spread to the corpus callosum ampulla, thalamus, and basal ganglia from 4 years of age (Figure 1D-F, K-M). Atrophy of the cerebrum and brainstem progressed rapidly after the age of 5 years (Figure 1G, N). Both missense variants were localized on the dehydrogenase unit (Supplemental Figure 1C).   According to the American College of Medical Genetics standards and guidelines, the variants were classified as likely pathogenic and uncertain significance, respectively (Supplemental Table S1).