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.

Interhypothalamic Adhesion: A Series of 13 Cases

“…Rhombencephalosynapsis is a midline cerebellar anomaly that can coexist with holoprosencephaly 12 ; partial rhombencephalosynapsis associated with Chiari II malformation was present in 1 patient. Additional midline anomalies outside the typical holoprosencephaly disease spectrum were also encountered in this case series.…”

Congenital Abnormalities of the Posterior Fossa

“…The majority of patients are nonsyndromic. However, rhombencephalosynapsis is a key feature of Gómez-López-Hernández syndrome (OMIM 601853 [parietal alopecia, trigeminal anesthesia, and craniofacial dysmorphic signs]) (32,33) and may be seen in patients with associated VACTERL (vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal fistula, renal anomalies, and limb defects) (34). The sporadic nature of rhombencephalosynapsis contributes to its low recurrence risk.…”

“…Long-term cognitive outcome varies from severe impairment to normalcy (32). Patients with more severe rhombencephalosynapsis, associated holoprosencephaly, or VACTERL features have more severe neurodevelopmental impairment (34). Systemic involvement is uncommon.…”

Gomez-Lopez-Hernández syndrome: First reported case from the Indian subcon-tinent

“…vertebral anomalies, anal atresia, cardiovascular anomalies, tracheaesophageal fistula, renal anomalies, and limb defects. More than 90 individuals with rhombencephalosynapsis have been reported in the literature, and 25 of those individuals were found to have GLHS (8). This indicates that rhombencephalosynapsis is a consistent finding in GLHS.…”