"Joubert Syndrome" Revisited: Key Ocular Motor Signs With Magnetic Resonance Imaging Correlation

Abstract

Joubert syndrome is characterized by episodic hyperpnea and apnea, developmental delay, hypotonia, truncal ataxia, ophthalmologic abnormalities, and vermian dysgenesis. We studied 15 patients with the diagnosis of Joubert syndrome to (1) more fully define the syndrome's clinical features, and (2) correlate the clinical features with magnetic resonance imaging (MRI) findings. Eight of 15 patients had a history of episodic hyperpnea and apnea. All patients had developmental delay and hypotonia. Of the 13 patients receiving detailed neuro-ophthalmologic evaluations, three had optic nerve dysplasia, pendular nystagmus, and gaze-holding nystagmus. All 13 patients had a normal vestibulo-ocular reflex based on head thrust, but had absent to poor ability to cancel the vestibulo-ocular reflex horizontally and vertically. Twelve of 13 patients had impaired smooth pursuit. Twelve of 13 patients had defects in initiation of saccades and quick phases. Two of the most consistent radiologic features were absent or hypoplastic posterior cerebellar vermis, and deformed midbrain and pontomesencephalic junction, which based on ocular motor physiology correlate with the vestibulo-ocular reflex cancellation/ pursuit defect and saccade initiation defect, respectively. As a result of midbrain, vermian, and superior cerebellar peduncle abnormalities, axial neuroimaging showed a unique "molar tooth" appearance of these structures. These results indicate that Joubert syndrome results from maldevelopment of the midbrain and cerebellar vermis, producing a pathognomonic sign on MRI.

Distinguishing the four genetic causes of jouberts syndrome–related disorders

“…Joubert syndrome is a severe developmental disorder mainly consisting of ataxia, oculomotor apraxia and mental retardation and characterized by cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the "molar tooth sign" 1,2 . Patients frequently display additional features of cystic kidney disease progressing to renal failure and ocular manifestations including retinopathy, encompassing the Joubert Syndrome Related Disorders (JSRD) group of conditions [3][4][5] .…”

Ophthalmological findings in Joubert syndrome

“…Our findings of ocular motor defects are in agreement with the findings of earlier studies. 4,7,9,10 Defects in smooth pursuit and VOR cancellation can be contributed to deformed cerebellar vermis. Saccades and quick phases of nystagmus are generated involving the brainstem.…”

“…1,2 Diagnostic criteria in JS include hypotonia, ataxia, global developmental delay, and the neuroradiological finding of 'molar tooth sign'. 3,4 The term 'JS-related disorders' was introduced referring to a group of pleiotropic conditions presenting the pathognomonic features of JS associated with variable involvement of other organs and systems. Almost all JS-related disorder genes, so far identified, encode for proteins expressed in the primary cilium or in the centrosome.…”

“…5 Ocular and oculomotor involvement is common in JS. 4,[6][7][8][9][10] However, findings differ considerably because of a wide range of phenotypic variability among patients with JS.…”

Cerebellar vermis hypoplasia - non progressive congenital ataxia: clinical and radiological findings in a pair of siblings

“…Steinlin et al 15 reviewing 34 subjects with NPCA found three pairs of siblings but only one child had vermis cerebellar hypoplasia as the only abnormality, since the other siblings had also hemispheres cerebellar hypoplasia or even normal cerebellum. Joubert's syndrome is a rare autosomal recessive condition and the criteria for the diagnosis has been outlined: irregular breathing in the neonatal period, developmental delay, mental retardation, hypotonia, ocular motor abnormalities, and, occasionally, retinal dystrophy and cystic kidneys associated with cerebellar malformation consisting in vermis hypoplasia or agenesis and abnormalities at the pontomesencephalic junction [16][17][18][19] . We describe the clinical and radiological findings of a pair of siblings and compare them with the literature.…”