Rhombencephalosynapsis: a hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity

Abstract

Rhombencephalosynapsis is a midline brain malformation characterized by missing cerebellar vermis with apparent fusion of the cerebellar hemispheres. Rhombencephalosynapsis can be seen in isolation or together with other central nervous system and extra-central nervous system malformations. Gómez-López-Hernández syndrome combines rhombencephalosynapsis with parietal/temporal alopecia and sometimes trigeminal anaesthesia, towering skull shape and dysmorphic features. Rhombencephalosynapsis can also be seen in patients with features of vertebral anomalies, anal atresia, cardiovascular anomalies, trachea-oesophageal fistula, renal anomalies, limb defects (VACTERL) association. Based on a comprehensive evaluation of neuroimaging findings in 42 patients with rhombencephalosynapsis, we propose a spectrum of severity, ranging from mild (the partial absence of nodulus, anterior and posterior vermis), to moderate (the absence of posterior vermis with some anterior vermis and nodulus present), to severe (the absence of posterior and anterior vermis with some nodulus present), to complete (the absence of the entire vermis including nodulus). We demonstrate that the severity of rhombencephalosynapsis correlates with fusion of the tonsils, as well as midbrain abnormalities including aqueductal stenosis and midline fusion of the tectum. Rhombencephalosynapsis is also associated with multiple forebrain abnormalities including absent olfactory bulbs, dysgenesis of the corpus callosum, absent septum pellucidum and, in rare patients, atypical forms of holoprosencephaly. The frequent association between rhombencephalosynapsis and aqueductal stenosis prompted us to evaluate brain magnetic resonance images in other patients with aqueductal stenosis at our institution, and remarkably, we identified rhombencephalosynapsis in 9%. Strikingly, subjects with more severe rhombencephalosynapsis have more severely abnormal neurodevelopmental outcome, as do subjects with holoprosencephaly and patients with VACTERL features. In summary, our data provide improved diagnostic and prognostic information, and support disruption of dorsal-ventral patterning as a mechanism underlying rhombencephalosynapsis.

Figure 1

Typical neuroradiological findings in RES. (A and B) Fusion of the cerebellar hemispheres with continuity of the cerebellar folia and white matter across the midline in Subject 9 (A) and Subject 18 (B). Note the abnormal shape of the fourth ventricle in A. The cerebellum is pear shaped in B, consistent with mild superior herniation. (C) Residual posterior vermis (white arrowhead points to uvula) in Subject 28. (D) Residual anterior vermis in Subject 28 (black arrowhead). (E) Substantial residual nodulus (black arrow) in Subject 18. (F) Hypoplastic residual nodulus (black arrow) in Subject 32. Note the residual posterior vermis (white arrow) that is continuous superiorly with the nodulus (black arrow), as well as ectopic tissue within the cerebral aqueduct at the level of the inferior colliculus. T = Tonsil. (A, C and D) axial T₂; (B) coronal T₂; (E and F) sagittal T₁.

Figure 2

Spectrum of severity in RES. (A–E) Complete RES without residual vermis in Subject 17. Note the absent septum pellucidum, aqueductal stenosis and intraventricular cysts (D). (F–J) Severe partial RES in Subject 2. The nodulus (arrow) is present and projects into the 4th ventricle on the coronal image (I) and the tonsils are fused (F). Note the absent septum pellucidum, narrow transverse diameter of the cerebellum and the small posterior fossa. (K–O) Moderate partial RES in Subject 18. The nodulus (arrow) and anterior vermis (black arrowhead) are present. Note the absent septum pellucidum in (N). (P–T) Mild partial RES in Subject 6. The nodulus (arrows) is present but deficient. Anterior (black arrowhead) and posterior (white arrowhead) vermis is also present. The primary fissure is indistinct on the sagittal images (E, J, O and T). (A–C, K–M and P–R) axial T₂ ranging from caudal to rostral; (F–H) axial T₁ ranging from caudal to rostral; (D, N and S) coronal T₂; (I) coronal T₁; (E, J, O and T) sagittal T₁. Lower case alphabets in E, J, O and T refer to the level of sections of the corresponding axial images labeled with upper case alphabets.

Figure 3

Aqueductal stenosis in RES. (A and B) Obstruction at the level of the superior colliculi (white arrow in A and black arrow in B), which are fused across the midline in Subject 29. Note the shunted hydrocephalus and severely dysgenetic corpus callosum with intact rostrum. (C and D) Obstruction at the level of the inferior colliculi (arrowheads), which are fused across the midline in Subject 8. Note the severe hydrocephalus with funnelling of the aqueduct, the retrocerebellar fluid collection and hypoplasia of the cerebellum and pons. (E and F) Obstruction at the junction of the aqueduct and fourth ventricle in Subject 2. The superior medullary velum is thickened (white arrow) and the superior cerebellar peduncles are angled medially. Note the mild inferior cerebellar ectopia in (E). Note the tiny focus of low signal within the superior aspect of the fourth ventricle (adjacent to the white arrow in F) and within the lateral ventricles in E is related to air from recent shunt manipulation. (G–I) Obstruction from the level of the thickened posterior commissure (bracket) to the level of the superior cerebellar peduncles with midline fusion of the superior colliculi (black arrow) in Subject 1. Note partial agenesis of the corpus callosum in (G) and the absence of hydrocephalus, despite complete obliteration of the cerebral aqueduct on imaging. Note also the severely hypoplastic mammillary bodies in Subjects 8, 2 and 1 (long white arrows in C, E and G). (A, C, E and G) sagittal T₁; (B, F and I) axial T₁; (D, H) axial T₂.

Figure 4

Ectopic cerebellar tissue and superior cerebellar peduncle configuration in RES. (A and B) Subject 34, partial RES. There is anterior vermis (arrows) that extends just posterior to the confluence of the superior cerebellar peduncles. The superior medullary velum is seen superior to the arrow in (B), and inferior to the inferior colliculus. (C and D) Subject 39, partial RES. There is anterior vermis that extends beyond the confluence of the superior cerebellar peduncles into the most caudal aspect of the cerebral aqueduct, reflecting a more severe pattern of ectopic tissue. No associated aqueductal stenosis. The superior medullary velum is not seen in this case, which may relate to the extent of the ectopic cerebellar tissue, in addition to thick slices. (E and F) Subject 17, complete RES. The anterior vermis is not visualized in this case, however, small ectopic tissue is seen at—and obscuring—the confluence of the superior cerebellar peduncles, which appear fused at the midline. This is causing obstruction at the most caudal aspect of the cerebral aqueduct. The superior medullary velum is present superior to the arrow in (F). After shunting, the subject developed an intraventricular cyst (asterisk).

Figure 5

Supratentorial abnormalities associated with RES. (A and B) Mass-like fusion of the mesencephalon, diencephalon and hypothalamus (A) with occipital holoprosencephaly (black arrow) and aplasia of the ventricles (B) in Subject 15. (C) Middle interhemispheric fusion (arrowhead) in Subject 14. (D) Absent olfactory bulbs in Subject 17 (white arrows). (A) coronal T₂; (B) axial T₁; (C) sagittal T₁; (D) axial T₂.