Figure 1

Figure 1

Pedigrees of the families with bi-allelic SNF8 variants and T2-weighted brain MRI scans of affected individuals with bi-allelic variants in SNF8

(A) Pedigrees of the families A–F. Variants identified in the individuals are depicted underneath the corresponding symbol. In family A, the healthy male sibling (II-1) of individuals A1 and A2 was not compound heterozygous for the SNF8 variants. In family D, the healthy female sibling (II-1) was not compound heterozygous for the SNF8 variants. Solid symbol, affected individual; circles, females; squares, males; slashed symbols, deceased.

(B) Brain MRI scans of the affected individuals with pathogenic variants of SNF8. (i–xii) T2-scans of the severely affected individuals. Images of A1 at the age of two (i, ii) and six months (iii, iv), of subject A2 at the age of two months (v, vi), of subject B1 at the age of four (vii, viii) and 15 months (ix, x), and of subject C2 at the age of one month (xi, xii). All severely affected subjects (i–xii) show a pronounced and persistent white matter hyperintensity, an atrophy of the cerebrum and callosal hypoplasia. The brainstem appears comparatively normal and the cerebellum is less severely affected. Pachygyria was noted in individual A2 (v). Note the rapidly progressive enlargement of the lateral ventricles due to cerebral white matter loss in subjects A1 and B. (xiii–xx) MRI images of the less severely affected individuals. Individuals D1 (xiii–xv) and E1 (xvi–xviii), both recorded at the age of 16 years, 3D volumetric T1 showing cerebellar atrophy (xiii and xvi, red arrows), as well as severe volume reduction of the anterior optic pathway including optic nerves, optic chiasm, and optic tracts (xiv and xvii, axial magnification of the 3D volumetric T1, red arrows). Moreover, on axial T2 (xv) or FLAIR (xviii) images, slight hyperintensity of the parieto-occipital white matter was observed (red arrows); notably automatic software evaluation (freesurfer) demonstrated a total cerebral white matter volume reduction in both affected individuals. (xix and xx) MRI scan of individual F1 at the age of two years showing normal myelination and white matter volume in T2 (xix) and a slightly dysmorphic callosal body as well as slight cerebellar atrophy in a sagittal T1 scan (xx, red arrow).