Clinical and Radiological Features Associated with Rhombencephalosynapsis
Clinical and Radiological Features Associated with Rhombencephalosynapsis
Abstract & Commentary
By Sotirios Keros, MD, PhD, Instructor, Department of Pediatrics, Division of Pediatric Neurology, Weill Cornell Medical College. Dr. Keros reports no financial relationships relevant to this field of study.
Synopsis: This study presents a large group of new cases of rhombencephalosynapsis and carefully describes correlations to other associated morphological abnormalities as well as to outcomes.
Source: Ishak GE, et al. Rhombencephalosynapsis: A hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity. Brain 2012;135:1370-1386.
Rhombencephalosynapsis (res) is a rare disorder of cerebellar formation, characterized by partial or complete loss of the vermis. As the name implies, in RES the left and right cerebellar hemispheres are fused. This is in contrast to other cerebellar vermian hypoplasia syndromes, such as Joubert syndrome or Dandy-Walker malformation, where the lobes remain separated. The pathogenesis is unknown, with most of the occurrences appearing de novo, but there is also evidence for autosomal recessive inheritance in a few cases.
RES can occur in isolation, but in Gomez-Lopez-Hernandez syndrome (GLH), RES is found together with parietal alopecia, trigeminal anesthesia, and can include dysmorphic facies, short stature, and skull shape abnormalities. Occasionally RES is found together with one or more features also found in VACTERL association (vertebral anomalies, anal defects, cardiovascular anomalies, tracheoesphageal fistula, renal/radial anomalies, and limb defects).
This study by Ishak et al describes 42 new cases of RES. Ten cases were found via review of the Seattle Children's Hospital imaging database of more than 15,000 reports by searching for RES. An additional five cases were found in the database after a re-review of 56 MRIs with aqueductal stenosis. Twenty-seven cases were obtained via referral from outside clinicians. The authors qualitatively evaluated several anatomical characteristics of the MRIs: the infratentorium for cerebellar size, shape, morphology and vermian deficiency pattern; the posterior fossa for size and fourth ventricle shape; the superior cerebellar peduncles for orientation and presence of ectopic tissue; the superior medullary velum for thickness and presence of ectopic tissue; the posterior commissure for thickness; the cerebral aqueduct for patency; the pons for size; the inferior and superior colliculi for fusion or presence of ectopic tissue; the supratentorium for interhemispheric fusion, migrational disorders, presence of the septum pellucidum, corpus callosal integrity, fusion of fornices, integrity of mammillary bodies, pituitary gland, and olfactory bulbs; and presence of ventriculomegaly.
Cases were grouped into four clinical categories 1) a diagnosis of GLH, 2) at least one VACTERL feature but not GLH, 3) RES which occurred together with holoprosencephaly who were not in the first two groups, and 4) RES not otherwise specified. Finally, cases were assessed a clinical outcome rating of mild, moderate, or severe based on an intake form and records review.
Whereas the existing literature typically has described RES as either partial or complete, the authors were able to identify a spectrum in the pattern and severity of cerebellar fusion. In general, mild cases involved only the posterior vermis (in approximately 30%), while the anterior vermis and then the nodulus were also fused or absent in the moderate (20%) and severe cases (20%) respectively, with complete absence of all parts of the vermis (20%) or an atypical pattern (10%) in the remaining cases.
The severity of RES and severity of outcome were correlated. In addition, outcomes were worse in the clinical categories of either RES with holoprosencephaly and RES with VACTERL compared to those in the GLH or RES NOS category. However, the severity of RES did not correlate with clinical category. There were no significant sex-specific differences.
The authors describe several non-vermian abnormalities found in conjunction with RES. The posterior fossa was generally small, and small size correlated with severity of RES. The pons was variably flat, hypoplastic, or had a compressed appearance. In complete RES, the cerebellum tended to be hypoplatstic. In contrast, in more than half the cases of partial RES, the cerebellum extended upward through the supratentorial notch while inferior cerebellar ectopia (i.e., Chiari I malformation) was present in about a third of the cases. This was attributed to a normal cerebellar size in an otherwise small posterior fossa.
Approximately half of the cases had aqueductal stenosis, which was strongly associated with fusion of midbrain structures at the level of the stenosis such as the inferior or superior colliculi. This fusion occurred across the midline, in the craniocaudal direction, or both. Aqueductal stenois was also associated with superior cerebellar peduncles that were too close to the midline. Nineteen of the cases with aqueductal stenosis required shunting due to obstructive hydrocephalus. Ventriculomegaly was not correlated with the severity of RES; however, it was correlated with worse clinical outcome.
The study identified the presence of several forebrain abnormalities. More than half the cases had an absent septum pellucidum and three quarters had a thin, dysplastic, or otherwise abnormal corpus callosum. Many cases had absent mammillary bodies (30%), fused fornices (50%), or absent olfactory bulbs (30%). Although these types of forebrain abnormalities can be secondary to a destructive process resulting from hydrocephalus, the authors attribute the findings to a developmental defect, given that these features were also seen in those without hydrocephalus. In addition, prenatal imaging was available for some cases, which confirmed the abnormality prior to the development of hydrocephalus.
Seven patients had cortical abnormalities: two with bilateral frontal polymicrogyria with heterotopia, two with periventricular heterotopia, and three with holoprosencephaly. Two of the subjects had an unusual form of holoprosencephaly with fusion of occipital lobes, thalami, basal ganglia, and hypothalamus.
Commentary
The new cases of RES described in this study provide significant new information on this rare disorder. Patients with aqueductal stenosis should be carefully evaluated for RES, with particular attention given to the posterior vermis so as not to miss the mild cases. The authors suggest that RES also should be sought in those with cerebellar herniation, a small cerebellum, and an absent septum pellucidum. Although it seems intuitive that those with severe or complete RES, or those with concomitant holoprosencephaly or VACTERL features will have worse outcomes, sampling bias somewhat limits the prognostic data. This is particularly true in mild cases, given we have limited information about the overall prevalence of RES.
Although the etiology is not known, RES clearly is not a disorder limited to the cerebellum, and this careful description of the spectrum of RES will help to identify additional cases. This hopefully will lead to an increased understanding of RES, including the identification and development of appropriate genetic mouse models of abnormal dorsal midline signaling.
This study presents a large group of new cases of rhombencephalosynapsis and carefully describes correlations to other associated morphological abnormalities as well as to outcomes.Subscribe Now for Access
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