Figure 2.

Brain images of affected individuals within the 6p25.3 cohort. (a–t) T₁-weighted midsagittal magnetic resonance images in two control subjects (a,b) and 18 subjects with 6p25.3 CNVs that include FOXC1 or intragenic mutations of FOXC1 (c–t). The midline cerebellar vermis (v) is marked only in the top row of images. The lower limit of the vermis typically extends down to the obex, marked by a horizontal white line in each image. In all but one individual (h), the lower border of the vermis does not reach the white line, indicative of cerebellar vermis hypoplasia (CVH). Asterisks (*) indicate an enlarged posterior fossa. In 5/6 individuals with large deletions of 6p25.3 (c–g), brain images show a small and upwardly rotated vermis, cystic dilatation of the fourth ventricle and an enlarged posterior fossa, meeting criteria for classic Dandy-Walker malformation (DWM). The remaining individual (h) unexpectedly has a normal or mildly enlarged vermis. The vermis appears abnormal in all four individuals with small deletions of 6p25.3 (i–l). The first two (i,j) meet criteria for DWM, although the abnormalities are less severe than in the subject with larger deletions. The next (k) has mild CVH with normal vermis position (not rotated upward), a normal fourth ventricle and mildly enlarged posterior fossa, consistent with mega-cisterna magna (MCM). The last individual in this group (l) has mild CVH only. The three individuals with heterozygous intragenic FOXC1 mutations (m–o) all have mild CVH only. Among the five individuals with 6p25.3 duplication, two sibs (p,t) have obvious MCM, whereas three other sibs—probably distantly related to the first two—have mild CVH only.