Gyanchand, V Chowdhury, R Dixit, S Singh
cerebellar peduncles, cerebellar vermis, isthmus, joubert's syndrome, molar- tooth sign, mri
Gyanchand, V Chowdhury, R Dixit, S Singh. Joubert Syndrome. The Internet Journal of Radiology. 2006 Volume 7 Number 1.
Joubert syndrome is a rare autosomal recessive congenital disorder having characteristic clinical features and imaging findings on Magnetic Resonance Imaging (MRI). The 'Molar Tooth' sign is uniformly seen in almost all cases, characterized by an abnormally deep interpeduncular fossa; elongated, thick, and mal-oriented superior cerebellar peduncles; and absent or hypoplastic cerebellar vermis on axial brain MRI through the junction of the midbrain and hindbrain (isthmus region). Supratentorial structures are unaffected, however corpus callosal agenesis and ventricular dilatation may be found in some cases. Two types of Joubert syndrome has been described on the basis o presence or absence of retinal involvement. The importance of recognizing Joubert syndrome is related to the outcome, its autosomal recessive trait, and the potential complications that may develop. Prenatal diagnosis by ultarsonography and antenatal MRI is also possible.
Joubert syndrome was first described by French neurologist Marie Joubert. Joubert syndrome is a rare disorder characterized by episodic hypernea, apnea, developmental delay, nystagmus, ataxia and hypotonia. This syndrome is a rare disorder inherited as an autosomal recessive trait.(1,2,3). Molar tooth sign, which was first described in Joubert syndrome, can be present in other syndromes recently referred to as cerebello-oculo- renal syndromes.
A 10 month old female patient was referred to our pediatric outpatient department with complaints of psychomotor delay, abnormal eye movement and episodes of hyperpnoea . Patient has undergone surgery for polydactyly in both the hands.
On physical examination developmental delay, hypotonia, prominent forehead, protruded tongue and hyperpnea was seen. The patient's sibling was diagnosed as having Joubert's syndrome 4 years before. A clinical diagnosis of Joubert's syndrome was made and patient was referred for MRI examination.
Multiplanar MR imaging of brain was performed on 1.5T magnet using dedicated circularly phased array head coil. T1 & T2 weighted images showed dysplasia of both superior cerebellar peduncles and thinning of the isthmic portion the brainstem at pontomesencephalic junction with deep inerpeduncular fossa resulting in typical ‘ Molar tooth' configuration. The sagittal T1 weighted images showed abnormal horizontally oriented and thickened superior cerebellar peduncles. The more inferior axial images reveal ‘batwing' configuration of the fourth ventricle. In addition the cerebellar vermis was absent with apposition of the cerebellar hemisphere in the midline. Supratentorial structures appear normal. The corpus callosum was normally developed.
Joubert syndrome is a rare genetic disorder that primarily affects the balance and coordination center of the brain. It is characterized by partial or complete absence of the cerebellar vermis and dysplastic development of the midbrain (4,5,6). This syndrome was first described by Marie Joubert and associates in 1969 in four siblings and one sporadic case that exhibited episodic hyperpnea, abnormal eye movements, ataxia and mental retardation with agenesis of cerebellar vermis(7) .
Maria et al. described other abnormalities in Joubert syndrome, such as ocular and oculomotor signs (n = 58, 95%), tongue protrusion (n = 26, 45%), polydactyly (n = 13, 23%), renal abnormalities (n = 9, 16%), megalocephalus (n = 7, 12%), microcephaly (n = 5, 9%), hepatic abnormalities (n = 2, 4%), bradycardia (n = 1, 2%), cardiac murmur (n = 1, 2%), cerebral palsy (n = 1, 2%), hypothalamic abnormalities (n = 1, 2%), and cleft lip (n = 1, 2%) .
In the syndrome, midline structures of the brain-stem have both anatomic and functional defects. Neuropathological studies reveal agenesis of cerebellar vermis, malformations of several brainstem nuclei and dysplasia of structures at the ponto-mesencephalic junction. Extensive brainstem malformation could explain the oculomotor apraxia and hyperpnea; anomalies of the gracile nuclei and solitary tract are thought to contribute to the abnormal respiratory pattern .
The eye abnormalities observed in this disease include complete oculomotor apraxia in horizontal and vertical directions and ocular coloboma . Inheritance of this disease is said to be autosomal recessive. Recent studies have shown that it is a genetically heterogenous disorder with one locus pointing to chromosome 9q [11,12]. Based on the presence or absence of retinal dystrophy, 2 types are described. Hypoplasia of the cerebellar vermis with clinical neonatal breathing abnormalities, oculomotor disorders, and hypotonia are present in type I. In addition to these, retinal and renal dysplastic changes are seen in type II, which has a worse prognosis [13,14]. The clinical history of delayed development, eye movement disorder with failure to develop vision, and abnormal breathing episodes, together with the imaging findings, is classic for Joubert syndrome.
The main imaging findings seen are partial or complete absence of vermis, thickened and abnormal orientation of the superior cerebellar peduncles, thinning of the isthmic portion of the brainstem with deep interpeduncular cistern producing the classical molar tooth sign. This sign has been reported in 85% patients of Joubert syndrome. This sign is caused by lack of normal decussation of the superior cerebellar peduncular fibres leading to enlargement of peduncles which follow a more horizontal course extending perpendicular to the brainstem between the midbrain and cerebellum (15). The absence of crossing fibres is also responsible for decreased anteroposterior diameter of the brainstem and deep interpeduncular cistern (16).The combination of these findings results in the classical molar tooth configuration on axial MR images of the midbrain. The absence of normal vermis creates a midline cleft between two normal appearing cerebellar hemispheres resulting in a characteristic ‘ batwing' appearance of the fourth ventricle on axial MR images (17).
The cerebrum is not affected, although moderate lateral ventricular enlargement due to atrophy has been was described in 6%–20% of cases, with corpus callosum dysgenesis present in 6%–10% (15,18).
Molar tooth sign is also seen in Varadi- Papp (oro-facial-digital type IV), COACH, Dekaban-Arima, and Senior-Löken syndromes. A Y-shaped metacarpus, cleft lip, cleft palate, and lingual nodule are also seen in Varadi-Papp syndrome. A Y-shaped metacarpus is characteristic of this syndrome. Oligophrenia, ataxia, coloboma, and hepatic fibrosis are seen in addition to cerebellar vermian hypoplasia in COACH syndrome. Renal and retinal pathologies are also seen in Dekaban-Arima and Senior-Löken syndromes, in addition to molar tooth sign, and distinguish them from type II Joubert syndrome, which has a poor prognosis .
The diagnosis is important for future procedures that require anesthesia (19). Patients with
Joubert syndrome is a rare congenital neurological disorder with autosomic recessive inheritance. The MRI findings in this disorder are characteristic with a very limited differential diagnosis. With typical clinical and imaging findings the diagnosis is easily made.
Dr Gyanchand Deptt. of Radiodiagnosis Lok Nayak Hospital & Maulana Azad Medical College New Delhi, India E mail: firstname.lastname@example.org