Magnetic resonance images of six individuals who are heterozygous for a recurrent p.Arg1740Trp pathogenic variant in SETD2. Sagittal T₁-weighted images (A, D, G, J, M, P), coronal T₂- (B, N) and T₁- (E, H, K) weighted images, and axial FLAIR images (C, F, I, L, O) are provided.

Patient 1 (A-C); male age six weeks

Patient 2 (D-F): male age four days

Patient 3 (G-I): newborn female

Patient 5 (J-L): female age six years

Patient 6 (M-O): male age four years

Patient 7 (P): male age two months

All affected individuals have low craniofacial ratios (corresponding to clinical microcephaly), as well as a foreshortened and thin corpus callosum (A, D, G, J, M, P). Thinning of the corpus callosum in A, D, G, and P could be due to a combination of callosal hypogenesis and unmyelinated state of white matter during the first few weeks of life. There is subtle overhanging appearance of the terminal portions of the frontal horns of the lateral ventricles relative to the striatum (best seen on coronal B and E). Gyri are somewhat simplified and sulci are shallow (C, F, I, and L). All affected individuals have cystic enlargement of the posterior fossa (mega cisterna magna) and prominent supracerebellar cisterns (A, D, G, and M). Slightly upturned hippocampi can be appreciated on coronal images (particularly in B, H, K, and N). Patient 1 has prominent convexity extra-axial spaces with left more than right subdural hemorrhage, which may be related to birth trauma. A cleft palate can be seen in D and G (small arrows). Patient 5 has white matter volume loss (K, L), with enlargement of the third and lateral ventricles. Patients 5, 6, and 7 have probable persistent Blake pouch cyst (J, N, P). Patients 3, 5, and 6 (G, J, M) demonstrate abnormality of anteroposterior midbrain-hindbrain patterning.

Reprinted from Rabin et al [2020]