Figure 2.

Neuropathological examination of the fetuses F.1-4 and F.2-1 and child F.2-2

(A–F) Posterior view (B) and basal view (A and C–F) of the brain showing cerebellar hypoplasia in affected individuals compared to stage-matched control individuals. Scale bar: 10 mm. Cerebella are outlined with white dashed lines. (B) An incomplete covering of the 4^th ventricle by the vermis is visible for the fetus F.1-4.

(G–L) Cross sections of the medulla stained with hematoxylin and eosin (HE) showing a fragmentation or extreme hypoplasia (arrows) of the olivary nuclei in affected individuals. Pyramidal tracts are clearly visible (^∗) and inferior olivary nuclei are noted (arrowhead) in control individuals. Scale bar: 500 μm.

(M–R) Horizontal (M) and sagittal (N–R) HE-stained sections showing a dysplasia and fragmentation of the dentate nucleus (arrows) in affected individuals. Arrowheads in control individuals point to the dentate nucleus. Scale bar: 500 μm.

(S–V) Sagittal HE-stained sections at the level of the vermis showing delayed lobulation with absence of tertiary foliation in the cerebellum of F.2-2 and hypoplasia severely affecting the anterior vermis (T and V). Primary fissures are indicated with arrowheads. Scale bar: 1 mm. Purkinje cell cluster heterotopia are visible in the white matter (T, top-left magnification).

(W–AB) Immunostaining of Purkinje cells with calbindin showing a decreased number and delayed maturation of Purkinje cells in the cerebellar cortex of affected individuals. Scale bar: 50 μm